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Information on EC 3.1.13.4 - poly(A)-specific ribonuclease
for references in articles please use BRENDA:EC3.1.13.4
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EC Tree 3 Hydrolases
3.1 Acting on ester bonds
3.1.13 Exoribonucleases producing 5′-phosphomonoesters
3.1.13.4 poly(A)-specific ribonuclease
IUBMB Comments
Cleaves poly(A) in either the single- or double-stranded form.
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
- 3.1.13.4
-
deadenylation
-
polya-specific
-
rna-binding
-
decapping
-
polyadenylation
-
polya-binding
- nocturnin
-
au-rich
-
mirna-mediated
-
telomere
-
trim
-
argonaute
- eif4e
-
pirnas
-
pumilio
- tristetraprolin
-
cap-binding
- congenita
-
exonucleolytic
-
p-bodies
-
dyskeratosis
-
oligoadenylation
-
pabps
- diagnostics
-
miriscs
- poly-a
-
are-binding
-
microrna-mediated
- medicine
-
eif4e-binding
showSynonyms
deadenylase, ccr4-not complex, parn, poly(a)-specific ribonuclease, rnase as, pnldc1, cytoplasmic deadenylase, poly(a) nuclease, 3'-exoribonuclease, poly(a) ribonuclease, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2',3'-exoribonuclease
-
-
-
-
3'-exoribonuclease
-
-
-
-
adenosine-specific exonuclease
nuclease, polyadenylate-specific exoribo-
-
-
-
-
PAB1P-dependent poly(A)-nuclease
-
-
-
-
PARN
PARN-1
PARN-like domain-containing protein 1
PF2046
PNLDC1
poly(A)-specific 3'-5' ribonuclease
poly(A)-specific 3'-exoribonuclease
-
-
-
-
poly(A)-specific mRNA exoribonuclease
-
-
-
-
poly(A)-specific ribonuclease
poly(A)-specific RNase
RNase H
additional information
PARN
-
-
PARN
-
additional information
-
the enzyme belongs to the family of RNAse D nucleases
additional information
-
similar enzyme: ribonuclease A, pancreatic ribonuclease A cleaves poly(A)-RNA only when aggregated
additional information
-
the enzyme belongs to the family of RNAse D nucleases
additional information
-
the enzyme belongs to the EEP family adopts a complete alpha/beta sandwich fold typical of hydrolases with highly conserved active site residues similar to APE1
additional information
poly(A)-specific ribonuclease belongs to the DEDD superfamily of 3'-exonucleases
additional information
-
similar enzyme: PAN: PAB-dependent poly(A) ribonuclease
additional information
-
similar enzyme: PAN: PAB-dependent poly(A) ribonuclease
additional information
-
similar enzyme: PAN: PAB-dependent poly(A) ribonuclease
additional information
-
the enzyme belongs to the family of RNAse D nucleases
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
exonucleolytic cleavage of poly(A) to 5'-AMP
-
-
-
-
exonucleolytic cleavage of poly(A) to 5'-AMP
mechansim, substrate recognition of mRNA for degradation
-
exonucleolytic cleavage of poly(A) to 5'-AMP
catalytic mechanism for CNOT6L 3'-5' deadenylation involving a pentacovalent phosphate transition, overview
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
hydrolysis of phosphoric ester
-
-
-
-
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CAS REGISTRY NUMBER
COMMENTARY
110541-21-4
-
215797-47-0
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(A)12 + H2O
AMP
Substrates: -
Products: full degradation of substrate
Products: full degradation of substrate
?
2',5'-linked oligoadenylates + H2O
5'-AMP
-
Substrates: in interferon treated cells
Products: -
Products: -
?
AAAACAAAAA + H2O
AMP + ?
Substrates: -
Products: plus a further degradation product containing four A nucleotides and one C nucleotide
Products: plus a further degradation product containing four A nucleotides and one C nucleotide
?
poly(A) + H2O
5'-AMP + ?
Substrates: average substrate length about 200 A
Products: -
Products: -
?
poly(A) + H2O
AMP + ?
Substrates: -
Products: no accumulation of polynucleotides
Products: no accumulation of polynucleotides
?
poly(A)18 RNA + H2O
5'-AMP + ?
-
Substrates: i.e. 18-nt poly(A) sequences are added to a 56-nt vector sequence, substrae of isoform AHG2
Products: -
Products: -
?
poly(A)25 RNA + H2O
5'-AMP + ?
-
Substrates: i.e. 25-nt poly(A) sequences are added to a 56-nt vector sequence, substrae of isoform AHG2
Products: -
Products: -
?
polyadenylated human telomerase RNA component + H2O
human telomerase RNA component + 5'-AMP
Substrates: -
Products: -
Products: -
?
polyadenylated RNA containing AU-rich elements + H2O
RNA containing AU-rich elements + AMP
Substrates: -
Products: -
Products: -
?
18S-E pre-rRNA + H2O
?
Substrates: different 18S-E pre-rRNAs
Products: -
Products: -
?
miR-362-5p + H2O
?
Substrates: miR-362-5p is defined by DROSHA and DICER to 26 nt in length
Products: -
Products: -
?
miR-362-5p + H2O
?
Substrates: a mammalian miRNA whose precursor contains a relatively large bulge compared with other premiRNAs. Primer extension analysis of miR-362-5p
Products: -
Products: -
?
mRNA-poly(A) + H2O
5'-AMP + ?
Substrates: fluorescently labeled RNA with a CCUUUCC sequence followed by a 9 nucleotide-long poly(A) tail
Products: -
Products: -
?
mRNA-poly(A) + H2O
?
Substrates: the enzyme is involved in the removal of polyA tails from mRNAs
Products: -
Products: -
?
mRNA-poly(A) + H2O
?
Substrates: nocturnin removes the poly(A) tail from a synthetic RNA substrate in a process known as deadenylation. It specifically degrades the 3' poly(A) tail
Products: -
Products: -
?
poly(A) RNA + H2O
5'-AMP + ?
-
Substrates: no activity on poly(U), poly(C), 23rRNA
Products: -
Products: -
?
poly(A) RNA + H2O
5'-AMP + ?
-
Substrates: exonucleolytic cleavage of poly(A) in either the single- or double-stranded form (poly(A)*poly(U)) to 5'-AMP (3'-exonucleolytic activity)
Products: -
Products: -
?
poly(A) RNA + H2O
5'-AMP + ?
-
Substrates: does not disintegrate polyribosomes isolated from quail oviduct
Products: -
Products: -
?
poly(A) RNA + H2O
5'-AMP + ?
-
Substrates: one RNA-binding domain is required for the substrate binding, but not for the catalysis of PARN
Products: -
Products: -
?
poly(A) RNA + H2O
5'-AMP + ?
-
Substrates: the RRM of PARN binds RNA
Products: -
Products: -
?
poly(A) RNA + H2O
5'-AMP + ?
-
Substrates: -
Products: -
Products: -
?
poly(A)-mRNA + H2O
5'-AMP
-
Substrates: in single- or double-stranded form
Products: -
Products: -
?
poly(A)-mRNA + H2O
5'-AMP
-
Substrates: no activity on xyloadenosine analogue
Products: -
Products: -
?
poly(A)-mRNA + H2O
5'-AMP
Substrates: DAN involved in oocyte maturation
Products: -
Products: -
?
poly(A)-mRNA + H2O
5'-AMP
-
Substrates: in single- or double-stranded form
Products: -
Products: -
?
poly(A)-mRNA + H2O
5'-AMP
-
Substrates: PAN mutants have only mild effects on deadenylation
Products: -
Products: -
?
poly(A)-mRNA + H2O
5'-AMP
-
Substrates: PAN RNase does not cut poly(A)tails to lengths below 50 adenylate residues
Products: -
Products: -
?
poly(A)-mRNA + H2O
5'-AMP
-
Substrates: controls poly(A)tail length
Products: -
Products: -
?
poly(A)-mRNA + H2O
5'-AMP
-
Substrates: absolute requirement for a ribonucleoprotein
Products: -
Products: -
?
poly(A)-mRNA + H2O
5'-AMP
-
Substrates: DAN involved in oocyte maturation
Products: -
Products: -
?
poly(A)-poly(U) + H2O
5'-AMP + ?
-
Substrates: double-stranded form
Products: -
Products: -
?
poly(A)-poly(U) + H2O
5'-AMP + ?
-
Substrates: double-stranded form
Products: -
Products: -
?
additional information
?
-
-
Substrates: mRNA deadenylation by exoribonucleolytic activity of PARN is essential for embryogenesis and viability, deadenylation of mRNA is often the first and rate-limiting step in mRNA decay, loss of the enzyme affects poly(A) tail length distribution of only a select subset of embryonic transcripts
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is 5-6 times more active if the substrate is m7G(5)ppp(5)G capped
Products: -
Products: -
?
additional information
?
-
-
Substrates: mRNA deadenylation by exoribonucleolytic activity of PARN is not essential for embryogenesis and viability
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is 5-6 times more active if the substrate is m7G(5)ppp(5)G capped
Products: -
Products: -
?
additional information
?
-
-
Substrates: physiological role of enzyme, recognition mechanisms that target mRNA for degradation
Products: -
Products: -
?
additional information
?
-
-
Substrates: PARN specifically degrades the mRNA poly(A) tails with a free 3'-hydroxyl group and releases 5'-AMP as the mononucleotide product
Products: -
Products: -
?
additional information
?
-
Substrates: PARN interacts not only with the 3'-end of the mRNA but also with its 5'-end as PARN contains an RNA-recognition motif domain that specifically binds both the poly(A) tail and the 7-methylguanosine cap. The interaction of PARN with the 5'-cap of mRNAs stimulates the deadenylation activity and enhances the processivity of this reaction
Products: -
Products: -
?
additional information
?
-
-
Substrates: the nuclease domain of CNOT6L exhibits full Mg2+-dependent deadenylase activity with strict poly(A) RNA substrate specificity. The active site of CNOT6L recognizes the RNA substrate through its negatively charged surface
Products: -
Products: -
?
additional information
?
-
Substrates: Poly(A)-specific ribonuclease is a eukaryotic enzyme that efficiently degrades mRNA poly(A) tails
Products: -
Products: -
?
additional information
?
-
-
Substrates: Poly(A)-specific ribonuclease is a eukaryotic enzyme that efficiently degrades mRNA poly(A) tails
Products: -
Products: -
?
additional information
?
-
-
Substrates: full-length CNOT6L shows 3'-5' deadenylase activity, the enzyme exhibits a molecular deadenylase mechanism involving a pentacovalent phosphate transition. The 3'-5' deadenylase activity of the CNOT6L catalytic domain alone for poly(A) RNA substrates appears to be increased with 7 nucleotides at the 5' end, or reduced with 25 nucleotides at the 5' end, substrate specificity, overview
Products: -
Products: -
?
additional information
?
-
Substrates: active site structure, modelling, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: synthesis of RNA substrates A5 to A20, G20, C20, U20, AAA, GGG, CCC, UUU, AXX, XXA, XAX, AXA, AAX, and XAA, where X denotes G, C, or U, and usage of commercial substrate, a 44-nucleotide heteropolymeric RNA, with sequence 5'-CCA UCU CAU CCC UGC GUG UCC CAU CUG UUC CCU CCC UGU CUC AG-3', substrate specificity of the recombinant enzyme, overview. The active site of PARN per se harbors specificity for recognition of adenosine
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is involved in processing of microRNA. Upon leavage of the 3' arm of the pre-miR-451 precursor hairpin by Argonaute2, the 3' end of the cleaved pre-miR-451 intermediate is then trimmed to the mature length by poly(A)-specific ribonuclease PARN. Trimming requires a 3'-5' exonucleolytic activity, prefers adenosine to uridine and depends on the presence of Mg2+
Products: -
Products: -
?
additional information
?
-
Substrates: shortening of the poly(A) tail is performed by the multi-subunit Ccr4-Not deadenylase, which contains the Caf1 (Pop2) and Ccr4 catalytic components, and poly(A)-specific ribonuclease (PARN)
Products: -
Products: -
?
additional information
?
-
Substrates: shortening of the poly(A) tail is performed by the multi-subunit Ccr4-Not deadenylase, which contains the Caf1 (Pop2) and Ccr4 catalytic components, and poly(A)-specific ribonuclease (PARN)
Products: -
Products: -
?
additional information
?
-
-
Substrates: shortening of the poly(A) tail is performed by the multi-subunit Ccr4-Not deadenylase, which contains the Caf1 (Pop2) and Ccr4 catalytic components, and poly(A)-specific ribonuclease (PARN)
Products: -
Products: -
?
additional information
?
-
Substrates: Poly(A)-specific ribonuclease (PARN) is a deadenylase that processes mRNAs and non-coding RNA
Products: -
Products: -
?
additional information
?
-
-
Substrates: Poly(A)-specific ribonuclease (PARN) is a deadenylase that processes mRNAs and non-coding RNA
Products: -
Products: -
?
additional information
?
-
Substrates: molecular mechanism of 5' cap recognition by PARN, overview. The PARN cap-binding site is bipartite: Trp475 constitutes the essential binding surface for m7G, while the first transcribed nucleoside is bound by the nuclease domain. The enzyme interacts with m7GpppG, m7Gpppm2'OG, m7GTP, GpppG(macro), GpppG(micro), m2_2.7GTP, and m3_2.2.7GTP. Role of His449 in mRNA 5' cap binding, involvement of His449 in sustaining the proper specificity of the enzyme, overview
Products: -
Products: -
?
additional information
?
-
Substrates: usage of synthetic oligoRNA substrates: N9A15, A12, U12, C12, G12 and dA12. Activity modulation experiments in the presence of m7G(5')ppp(5')G cap analogue. The recombinant enzyme exhibits specific deadenylation activity in vitro, with very high specificity for recognition of poly(A) or poly(dA)
Products: -
Products: -
?
additional information
?
-
-
Substrates: usage of synthetic oligoRNA substrates: N9A15, A12, U12, C12, G12 and dA12. Activity modulation experiments in the presence of m7G(5')ppp(5')G cap analogue. The recombinant enzyme exhibits specific deadenylation activity in vitro, with very high specificity for recognition of poly(A) or poly(dA)
Products: -
Products: -
?
additional information
?
-
Substrates: enzyme PARN performs exonucleolytic trimming of 18S-E pre-rRNA, and PARN can process the corresponding ITS1 RNA fragment in vitro
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme PARN performs exonucleolytic trimming of 18S-E pre-rRNA, and PARN can process the corresponding ITS1 RNA fragment in vitro
Products: -
Products: -
?
additional information
?
-
Substrates: PARN is one of the major mammalian 3'-specific exoribonucleases involved in the degradation of the mRNA poly(A)-tail and it is also involved in the regulation of translation in early embryonic development, it is the key enzyme involved in the deadenylation of mRNA in a cap-dependent manner
Products: -
Products: -
?
additional information
?
-
-
Substrates: PARN is one of the major mammalian 3'-specific exoribonucleases involved in the degradation of the mRNA poly(A)-tail and it is also involved in the regulation of translation in early embryonic development, it is the key enzyme involved in the deadenylation of mRNA in a cap-dependent manner
Products: -
Products: -
?
additional information
?
-
Substrates: the interaction between PARN and the 7-methylguanosine cap of mRNA plays a key role in stimulating the rate of deadenylation
Products: -
Products: -
?
additional information
?
-
-
Substrates: the interaction between PARN and the 7-methylguanosine cap of mRNA plays a key role in stimulating the rate of deadenylation
Products: -
Products: -
?
additional information
?
-
Substrates: PARN is a divalent metal ion-dependent 3'-exonuclease that specifically catalyzes the 3'-5'-degradation of the single-stranded poly(A) tail of mRNA with a free 3'-hydroxyl group
Products: -
Products: -
?
additional information
?
-
-
Substrates: PARN is a divalent metal ion-dependent 3'-exonuclease that specifically catalyzes the 3'-5'-degradation of the single-stranded poly(A) tail of mRNA with a free 3'-hydroxyl group
Products: -
Products: -
?
additional information
?
-
-
Substrates: PARN protein levels are not appreciably altered by lipopolysaccharide stimulation in RAW264.7 macrophage cells
Products: -
Products: -
?
additional information
?
-
Substrates: usage of synthetic oligoRNA substrates: N9A15, A12, U12, C12, G12 and dA12. Activity modulation experiments in the presence of m7G(5')ppp(5')G cap analogue. The recombinant enzyme exhibits specific deadenylation activity in vitro, with very high specificity for recognition of poly(A) or poly(dA)
Products: -
Products: -
?
additional information
?
-
-
Substrates: usage of synthetic oligoRNA substrates: N9A15, A12, U12, C12, G12 and dA12. Activity modulation experiments in the presence of m7G(5')ppp(5')G cap analogue. The recombinant enzyme exhibits specific deadenylation activity in vitro, with very high specificity for recognition of poly(A) or poly(dA)
Products: -
Products: -
?
additional information
?
-
Substrates: enzyme shows strong specificity toward polyadenylate nucleotides, no degradation of poly(C), poly(G), and poly(U) substrates
Products: -
Products: -
?
additional information
?
-
Substrates: RNase H fold protein PF2046 of Pyrococcus furiosus is a 3'-5' ssDNA exonuclease that cleaves after the second nucleotide from the 3' end of ssDNA and prefers poly-dT over poly-dA as a substrate
Products: -
Products: -
?
additional information
?
-
Substrates: RNase H fold protein PF2046 of Pyrococcus furiosus is a 3'-5' ssDNA exonuclease that cleaves after the second nucleotide from the 3' end of ssDNA and prefers poly-dT over poly-dA as a substrate
Products: -
Products: -
?
additional information
?
-
Substrates: RNase H fold protein PF2046 of Pyrococcus furiosus is a 3'-5' ssDNA exonuclease that cleaves after the second nucleotide from the 3' end of ssDNA and prefers poly-dT over poly-dA as a substrate
Products: -
Products: -
?
additional information
?
-
Substrates: RNase H fold protein PF2046 of Pyrococcus furiosus is a 3'-5' ssDNA exonuclease that cleaves after the second nucleotide from the 3' end of ssDNA and prefers poly-dT over poly-dA as a substrate
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme plays an important role in the posttranscriptional maturation of mRNA poly(A) tails, factors involved in positive, e.g. Pan3p, and negative, e.g. Pbp1p, regulation, schematic model, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: the poly(A)-binding protein, Pab1, and PAN, a poly(A) nuclease complex recruited by Pab1, connect mRNA biogenesis and 3' processing to export, Pab1p is essential, but several bypass suppressors exist, deletion leads to exosome-dependent retention at sites of transcription and inefficient nRNA release, e.g. of SSA4 mRNA, Pab1p and PAN interaction mechanism, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: protein-protein interaction specificity, Pab1p interacts with Pan3p and Pbp1p, which also interact with each other, Pbp1p interacts with itself, binding pocket structures, overview
Products: -
Products: -
?
additional information
?
-
-
Substrates: mRNA deadenylation by exoribonucleolytic activity of PARN is not essential for embryogenesis and viability
Products: -
Products: -
?
additional information
?
-
-
Substrates: isozyme PARN-1 degrades RNA-A60. No activity with RNA-A60 with a 22-heteronucleotide sequence added 3' to the poly(A) tail of RNA-A60 as substrate
Products: -
Products: -
?
additional information
?
-
-
Substrates: isozyme PARN-1 degrades RNA-A60. No activity with RNA-A60 with a 22-heteronucleotide sequence added 3' to the poly(A) tail of RNA-A60 as substrate
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is 5-6 times more active if the substrate is m7G(5)ppp(5)G capped
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
miR-362-5p + H2O
?
Substrates: miR-362-5p is defined by DROSHA and DICER to 26 nt in length
Products: -
Products: -
?
mRNA-poly(A) + H2O
?
Substrates: the enzyme is involved in the removal of polyA tails from mRNAs
Products: -
Products: -
?
poly(A) RNA + H2O
5'-AMP + ?
-
Substrates: no activity on poly(U), poly(C), 23rRNA
Products: -
Products: -
?
poly(A) RNA + H2O
5'-AMP + ?
-
Substrates: exonucleolytic cleavage of poly(A) in either the single- or double-stranded form (poly(A)*poly(U)) to 5'-AMP (3'-exonucleolytic activity)
Products: -
Products: -
?
poly(A) RNA + H2O
5'-AMP + ?
-
Substrates: does not disintegrate polyribosomes isolated from quail oviduct
Products: -
Products: -
?
poly(A) RNA + H2O
5'-AMP + ?
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: mRNA deadenylation by exoribonucleolytic activity of PARN is essential for embryogenesis and viability, deadenylation of mRNA is often the first and rate-limiting step in mRNA decay, loss of the enzyme affects poly(A) tail length distribution of only a select subset of embryonic transcripts
Products: -
Products: -
?
additional information
?
-
-
Substrates: mRNA deadenylation by exoribonucleolytic activity of PARN is not essential for embryogenesis and viability
Products: -
Products: -
?
additional information
?
-
-
Substrates: physiological role of enzyme, recognition mechanisms that target mRNA for degradation
Products: -
Products: -
?
additional information
?
-
-
Substrates: PARN specifically degrades the mRNA poly(A) tails with a free 3'-hydroxyl group and releases 5'-AMP as the mononucleotide product
Products: -
Products: -
?
additional information
?
-
Substrates: PARN interacts not only with the 3'-end of the mRNA but also with its 5'-end as PARN contains an RNA-recognition motif domain that specifically binds both the poly(A) tail and the 7-methylguanosine cap. The interaction of PARN with the 5'-cap of mRNAs stimulates the deadenylation activity and enhances the processivity of this reaction
Products: -
Products: -
?
additional information
?
-
-
Substrates: the nuclease domain of CNOT6L exhibits full Mg2+-dependent deadenylase activity with strict poly(A) RNA substrate specificity. The active site of CNOT6L recognizes the RNA substrate through its negatively charged surface
Products: -
Products: -
?
additional information
?
-
Substrates: Poly(A)-specific ribonuclease is a eukaryotic enzyme that efficiently degrades mRNA poly(A) tails
Products: -
Products: -
?
additional information
?
-
-
Substrates: Poly(A)-specific ribonuclease is a eukaryotic enzyme that efficiently degrades mRNA poly(A) tails
Products: -
Products: -
?
additional information
?
-
-
Substrates: enzyme is involved in processing of microRNA. Upon leavage of the 3' arm of the pre-miR-451 precursor hairpin by Argonaute2, the 3' end of the cleaved pre-miR-451 intermediate is then trimmed to the mature length by poly(A)-specific ribonuclease PARN. Trimming requires a 3'-5' exonucleolytic activity, prefers adenosine to uridine and depends on the presence of Mg2+
Products: -
Products: -
?
additional information
?
-
Substrates: shortening of the poly(A) tail is performed by the multi-subunit Ccr4-Not deadenylase, which contains the Caf1 (Pop2) and Ccr4 catalytic components, and poly(A)-specific ribonuclease (PARN)
Products: -
Products: -
?
additional information
?
-
Substrates: shortening of the poly(A) tail is performed by the multi-subunit Ccr4-Not deadenylase, which contains the Caf1 (Pop2) and Ccr4 catalytic components, and poly(A)-specific ribonuclease (PARN)
Products: -
Products: -
?
additional information
?
-
-
Substrates: shortening of the poly(A) tail is performed by the multi-subunit Ccr4-Not deadenylase, which contains the Caf1 (Pop2) and Ccr4 catalytic components, and poly(A)-specific ribonuclease (PARN)
Products: -
Products: -
?
additional information
?
-
Substrates: Poly(A)-specific ribonuclease (PARN) is a deadenylase that processes mRNAs and non-coding RNA
Products: -
Products: -
?
additional information
?
-
-
Substrates: Poly(A)-specific ribonuclease (PARN) is a deadenylase that processes mRNAs and non-coding RNA
Products: -
Products: -
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additional information
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Substrates: PARN is one of the major mammalian 3'-specific exoribonucleases involved in the degradation of the mRNA poly(A)-tail and it is also involved in the regulation of translation in early embryonic development, it is the key enzyme involved in the deadenylation of mRNA in a cap-dependent manner
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additional information
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Substrates: PARN is one of the major mammalian 3'-specific exoribonucleases involved in the degradation of the mRNA poly(A)-tail and it is also involved in the regulation of translation in early embryonic development, it is the key enzyme involved in the deadenylation of mRNA in a cap-dependent manner
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additional information
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Substrates: the interaction between PARN and the 7-methylguanosine cap of mRNA plays a key role in stimulating the rate of deadenylation
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additional information
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Substrates: the interaction between PARN and the 7-methylguanosine cap of mRNA plays a key role in stimulating the rate of deadenylation
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additional information
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Substrates: PARN is a divalent metal ion-dependent 3'-exonuclease that specifically catalyzes the 3'-5'-degradation of the single-stranded poly(A) tail of mRNA with a free 3'-hydroxyl group
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additional information
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Substrates: PARN is a divalent metal ion-dependent 3'-exonuclease that specifically catalyzes the 3'-5'-degradation of the single-stranded poly(A) tail of mRNA with a free 3'-hydroxyl group
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additional information
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Substrates: PARN protein levels are not appreciably altered by lipopolysaccharide stimulation in RAW264.7 macrophage cells
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additional information
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Substrates: RNase H fold protein PF2046 of Pyrococcus furiosus is a 3'-5' ssDNA exonuclease that cleaves after the second nucleotide from the 3' end of ssDNA and prefers poly-dT over poly-dA as a substrate
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additional information
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Substrates: RNase H fold protein PF2046 of Pyrococcus furiosus is a 3'-5' ssDNA exonuclease that cleaves after the second nucleotide from the 3' end of ssDNA and prefers poly-dT over poly-dA as a substrate
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additional information
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Substrates: RNase H fold protein PF2046 of Pyrococcus furiosus is a 3'-5' ssDNA exonuclease that cleaves after the second nucleotide from the 3' end of ssDNA and prefers poly-dT over poly-dA as a substrate
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additional information
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Substrates: RNase H fold protein PF2046 of Pyrococcus furiosus is a 3'-5' ssDNA exonuclease that cleaves after the second nucleotide from the 3' end of ssDNA and prefers poly-dT over poly-dA as a substrate
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additional information
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Substrates: the enzyme plays an important role in the posttranscriptional maturation of mRNA poly(A) tails, factors involved in positive, e.g. Pan3p, and negative, e.g. Pbp1p, regulation, schematic model, overview
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additional information
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Substrates: the poly(A)-binding protein, Pab1, and PAN, a poly(A) nuclease complex recruited by Pab1, connect mRNA biogenesis and 3' processing to export, Pab1p is essential, but several bypass suppressors exist, deletion leads to exosome-dependent retention at sites of transcription and inefficient nRNA release, e.g. of SSA4 mRNA, Pab1p and PAN interaction mechanism, overview
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additional information
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Substrates: mRNA deadenylation by exoribonucleolytic activity of PARN is not essential for embryogenesis and viability
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ba2+
Ca2+
Cd2+
-
2 mM, activates reaction, can modulated the substrate length requirement
Co2+
Cu2+
K+
K3PO4
Mg2+
Mn2+
Na+
Sn2+
Zn2+
additional information
Co2+
-
2 mM, activates reaction, can modulated the substrate length requirement
K+
-
the binding of K+ to the entire RNA-recognition motif domain, which plays a central role in the allosteric communications of PARN regulation, leads to an increase of substrate-binding affinity but a decrease in the cooperativity of the substrate-binding site, while the binding of the cap analogue decreases both the catalytic efficiency and the substrate-binding affinity
K+
K+ is essential to PARN activity and acts as an allosteric activator of PARN with multiple binding sites. K+ induces additional regular secondary structures and enhances PARN stability against heat-induced inactivation, unfolding and aggregation
Mg2+
-
2 mM, activates reaction, can modulated the substrate length requirement
Mg2+
-
can protect PARN against thermal inactivation by increasing the midpoint of inactivation and decreasing the inactivation rate, protective effect is unique to Mg2+ in a concentration-dependent manner
Mg2+
-
the deadenylase activity of CNOT6L is strictly dependent on the presence of Mg2+
Mg2+
required, the active site of PARN contains four conserved acidic amino acid residues, D28, E30, D292 and D382, the latter being the most important, that coordinate two Mg2+ ions and are essential for the catalytic activity. These acidic residues form a negative charge cave that can bind with two Mg2+ ions. Cofactor Mg2+ is also important to PARN stability against inactivation induced by heat treatment, but promotes thermal aggregation at high temperatures. Mg2+ significantly decreases the rate but increases the aggregate size of the 54 kDa wild-type enzyme in a concentration-dependent manner. The metal cofactor binding or mutation induces changes in the microenvironments around Trp residues
Mg2+
two Mg2+ ions present in the active sites of the ribonucleases of multi-subunit Ccr4-Not deadenylase and are required for RNA cleavage
Mg2+
active site consists of two metal ions (MgA and MgB), residue D50 takes a central position by contacting both metal ions. MgA is also coordinated by E52 and D240, while D171 contacts MgB. Seven water molecules, three associated with MgA and four with MgB, complete the dual octahedral coordination spheres of the two ions
Mn2+
Mn2+ together with Mg2+ creates a fast and non-specific enzyme
additional information
PARN is a divalent metal ion-dependent 3'-exonuclease
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-hydroxy-3-(3-methylbutyl)-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
-
1-hydroxy-3-methyl-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
-
1-hydroxy-3-nonyl-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
-
1-hydroxy-3-pentyl-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
-
1-hydroxy-3-[(morpholin-4-yl)methyl]-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
-
1-hydroxy-7-(2-phenylethyl)-3-(3-phenylpropyl)-3,7-dihydro-1H-purine-2,6-dione
-
1-hydroxy-7-[(pyridin-2-yl)methyl]-3,7-dihydro-1H-purine-2,6-dione
-
1-hydroxy-7-[(thiophen-2-yl)methyl]-3,7-dihydro-1H-purine-2,6-dione
-
3-benzyl-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
-
3-decyl-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
-
3-dodecyl-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
-
3-ethyl-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
-
3-hydroxy-6,7,8,9-tetrahydropyrido[2,1-f]purine-2,4(1H,3H)-dione
-
3-[2-(dimethylamino)ethyl]-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
-
6-hydroxy-1-(2-phenylethyl)-1,4-dihydro-5H-imidazo[4,5-b]pyridin-5-one
-
7-benzyl-1-[(prop-2-en-1-yl)oxy]-3,7-dihydro-1H-purine-2,6-dione
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ADP
-
purine monophosphate (RMP) and diphosphate nucleotides (RDP) exhibit competitive inhibition, furthermore PARN does not discriminate whether there is ribose or deoxyribose in the nucleotides, Mg2+ releases the inhibition by RDPs and RTPs, but not by RMPs
ATP
-
purine triphosphate nucleotides (RTP) behave as non-competitive inhibitors, furthermore PARN does not discriminate whether there is ribose or deoxyribose in the nucleotides, Mg2+ releases the inhibition by RDPs and RTPs, but not by RMPs
cap analogue 7-methylguanosine(5')ppp(5')G
-
allosteric inhibitor of PARN in the presence of a physiological K+ concentration
deoxyATP
-
purine triphosphate nucleotides (RTP) behave as non-competitive inhibitors, furthermore PARN does not discriminate whether there is ribose or deoxyribose in the nucleotides, Mg2+ releases the inhibition by RDPs and RTPs, but not by RMPs
deoxyGTP
-
purine triphosphate nucleotides (RTP) behave as non-competitive inhibitors, furthermore PARN does not discriminate whether there is ribose or deoxyribose in the nucleotides, Mg2+ releases the inhibition by RDPs and RTPs, but not by RMPs
GDP
-
purine monophosphate (RMP) and diphosphate nucleotides (RDP) exhibit competitive inhibition, furthermore PARN does not discriminate whether there is ribose or deoxyribose in the nucleotides, Mg2+ releases the inhibition by RDPs and RTPs, but not by RMPs
GMP
-
purine monophosphate (RMP) and diphosphate nucleotides (RDP) exhibit competitive inhibition, furthermore PARN does not discriminate whether there is ribose or deoxyribose in the nucleotides, Mg2+ releases the inhibition by RDPs and RTPs, but not by RMPs
GNF-7
treatment of HeLa cells reduces miR-21-5p levels to around 35% compared to the controls
GTP
-
purine triphosphate nucleotides (RTP) behave as non-competitive inhibitors, furthermore PARN does not discriminate whether there is ribose or deoxyribose in the nucleotides, Mg2+ releases the inhibition by RDPs and RTPs, but not by RMPs
guanidine hydrochloride
-
full-length enzyme retains most of its activity at guanidine hydrochloride concentrations below 0.5 M, whereas an abrupt decrease of the activity of p54 and p46 is found when guanidine hydrochloride concentration is increased
Mg2+
-
behaves as a destabilizer of the overall structural stability of PARN, promotes thermal unfolding and aggregation at high temperatures
neomycin
-
antibiotic neomycin B inhibits approximately 80% of PARN activity at a concentration of 10 microg/ml
NSC-86353
substitution of the benzyl moiety with a methyl group at the N7 position (NSC-85703) reduces the inhibitory activity over 10fold
Poly(A)
strong inhibition of both spermidine- and polyadenylate-binding protein-activated hPAN complex
poly(C)
strong inhibition of spermidine-, slight inhibition of polyadenylate-binding protein-activated hPAN complex
purine nucleotides
-
purine triphosphate nucleotides (RTP) behave as non-competitive inhibitors while purine monophosphate (RMP) and diphosphate nucleotides (RDP) exhibit competitive inhibition, furthermore PARN does not discriminate whether there is ribose or deoxy-ribose in the nucleotides, Mg2+ releases the inhibition by RDPs and RTPs, but not by RMPs
-
synthetic fluoro-pyranosyl nucleosides
synthetic nucleoside analogues bearing a fluoroglucopyranosyl sugar moiety and benzoyl-modified cytosine or adenine as a base can effectively inhibit human PARN
-
Zn2+
enzyme is inhibited by high zinc concentration with only two ions and 1mM Zn2+
AMP
-
purine monophosphate (RMP) and diphosphate nucleotides (RDP) exhibit competitive inhibition, furthermore PARN does not discriminate whether there is ribose or deoxyribose in the nucleotides, Mg2+ releases the inhibition by RDPs and RTPs, but not by RMPs
EDTA
activity is completely lost when the ions are removed from the wild-type enzyme by incubation with 10mM
kanamycin A
-
50% inhibition by high nanomolar concentrations, competition with divalent metal ions
kanamycin B
-
50% inhibition by high nanomolar concentrations, competition with divalent metal ions
lividomycin
-
50% inhibition by high nanomolar concentrations, competition with divalent metal ions
neomycin B
-
50% inhibition by high nanomolar concentrations, inhibition is pH-dependent, competition with divalent metal ions
paromomycin
-
50% inhibition by high nanomolar concentrations, competition with divalent metal ions
tobramycin
-
50% inhibition by high nanomolar concentrations, competition with divalent metal ions
additional information
-
model of inhibition mechanism for aminoglycosides, competition with divalent metal ions
-
additional information
discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1. Possible interaction modes of 3-hydroxy-pyrimidine-2,4-dione compounds with two divalent metal ions in the active site of Caf1, overview
-
additional information
discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1. Possible interaction modes of 3-hydroxy-pyrimidine-2,4-dione compounds with two divalent metal ions in the active site of Caf1, overview
-
additional information
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discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1. Possible interaction modes of 3-hydroxy-pyrimidine-2,4-dione compounds with two divalent metal ions in the active site of Caf1, overview
-
additional information
-
stress like hyperosmolarity, heat shock, and glucose deprivation, inhibit the ability of Ccr4p/Pop2p/Notp to deadenylate mRNA
-
additional information
-
a poly(A) competitor inhibits RNA-A60 deadenylation by isozyme PARN-1, whereas a poly(C) competitor has no effect on RNA-A60 deadenylation
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
K+
-
allosteric activator of PARN and its truncated forms, optimal concentration is around 100 mM, with the increase of the K+ concentration, the enzyme reaches its Vmax at a much lower substrate concentration
polyadenylate-binding protein
or spermidine, required for activity of hPAN complex, cannot stimulate hPAN2 alone
-
tristetraprolin
required for degradation of polyadenylated RNA containing AU-rich elements
-
spermidine
or polyadenylate-binding protein, required for activity of hPAN2 and of hPAN complex
additional information
-
Bic-C activates CCR4-dependent deadenylation of specific mRNAs during early oogenesis. Bic-C binds specific segments of the Bic-C 50 untranslated region and negatively regulates its own expression by binding directly to NOT3/5, a component of the CCR4 core deadenylase complex. CCR4-HA and NOT3/5 form an RNase-resistant complex with Bic-C
-
additional information
p21 3'-UTR triggers the action of PARN in the AGS cells
-
additional information
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p21 3'-UTR triggers the action of PARN in the AGS cells
-
additional information
PARN interacts with the 7-methylguanosine cap, which enhances its deadenylation activity
-
additional information
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PARN interacts with the 7-methylguanosine cap, which enhances its deadenylation activity
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Adenocarcinoma
Human Ccr4 and Caf1 Deadenylases Regulate Proliferation and Tumorigenicity of Human Gastric Cancer Cells via Modulating Cell Cycle Progression.
Alveolitis, Extrinsic Allergic
Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive.
Arthritis
The Acute-phase Response Is Not Predictive for the Development of Arthritis in Seropositive Arthralgia - A Prospective Cohort Study.
Bone Marrow Failure Disorders
Bone marrow failure and developmental delay caused by mutations in poly(A)-specific ribonuclease (PARN).
Breast Neoplasms
A feedback mechanism between PLD and deadenylase PARN for the shortening of eukaryotic poly(A) mRNA tails that is deregulated in cancer cells.
Breast Neoplasms
IMP1 regulates UCA1-mediated cell invasion through facilitating UCA1 decay and decreasing the sponge effect of UCA1 for miR-122-5p.
Carcinoma
Deciphering tissue-based proteome signatures revealed novel subtyping and prognostic markers for thymic epithelial tumors.
Carcinoma, Squamous Cell
Deciphering tissue-based proteome signatures revealed novel subtyping and prognostic markers for thymic epithelial tumors.
Congenital Bone Marrow Failure Syndromes
Poly (A)-specific ribonuclease (PARN): More than just "mRNA stock clearing".
Cysts
twin, a CCR4 homolog, regulates cyclin poly(A) tail length to permit Drosophila oogenesis.
Dyskeratosis Congenita
CD8+ T-cell senescence and skewed lymphocyte subsets in young Dyskeratosis Congenita patients with PARN and DKC1 mutations.
Dyskeratosis Congenita
Multiple bilateral hip fractures in a patient with dyskeratosis congenita caused by a novel mutation in the PARN gene.
Dyskeratosis Congenita
PARN modulates Y RNA stability, 3' end formation and its modification.
Dyskeratosis Congenita
Poly(A)-specific ribonuclease (PARN) mediates 3'-end maturation of the telomerase RNA component.
Dyskeratosis Congenita
Poly(A)-specific ribonuclease deficiency impacts telomere biology and causes dyskeratosis congenita.
Dyskeratosis Congenita
Poly(A)-specific ribonuclease is a nuclear ribosome biogenesis factor involved in human 18S rRNA maturation.
Dyskeratosis Congenita
Posttranscriptional modulation of TERC by PAPD5 inhibition rescues hematopoietic development in dyskeratosis congenita.
Dyskeratosis Congenita
The RNase PARN Controls the Levels of Specific miRNAs that Contribute to p53 Regulation.
Eye Neoplasms
The CCR4-NOT complex is a tumor suppressor in Drosophila melanogaster eye cancer models.
Fibrosarcoma
Comparison of ex vivo harvested and in vitro cultured materials from Echinococcus granulosus by measuring expression levels of five genes putatively involved in the development and maturation of adult worms.
Genetic Diseases, Inborn
Idiopathic Pulmonary Fibrosis: A Genetic Disease That Involves Mucociliary Dysfunction of the Peripheral Airways.
Genetic Diseases, Inborn
The RNase PARN Controls the Levels of Specific miRNAs that Contribute to p53 Regulation.
Heart Failure
The CCR4-NOT deadenylase complex controls Atg7-dependent cell death and heart function.
Hypersensitivity
Ccr4-not complex mRNA deadenylase activity contributes to DNA damage responses in Saccharomyces cerevisiae.
Idiopathic Interstitial Pneumonias
Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive.
Idiopathic Pulmonary Fibrosis
From incomplete penetrance with normal telomere length to severe disease and telomere shortening in a family with monoallelic and biallelic PARN pathogenic variants.
Idiopathic Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis: A Genetic Disease That Involves Mucociliary Dysfunction of the Peripheral Airways.
Idiopathic Pulmonary Fibrosis
Poly(A)-specific ribonuclease (PARN) mediates 3'-end maturation of the telomerase RNA component.
Idiopathic Pulmonary Fibrosis
Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive.
Idiopathic Pulmonary Fibrosis
[A rare familial form of idiopathic pulmonary fibrosis with Poly(A)-specific ribonuclease (PARN) mutation].
Infections
Alteration of nuclear (2'-5')oligoriboadenylate synthetase and nuclease activities preceding replication of human immunodeficiency virus in H9 cells.
Leukemia
Alterations of deadenylase expression in acute leukemias: evidence for poly(a)-specific ribonuclease as a potential biomarker.
Liver Cirrhosis
Whole-Exome Sequencing in Adults With Chronic Kidney Disease: A Pilot Study.
Lung Diseases, Interstitial
Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive.
Lung Neoplasms
Poly(A)-specific ribonuclease and Nocturnin in squamous cell lung cancer: prognostic value and impact on gene expression.
Lyme Disease
The proofreading domain of Escherichia coli DNA polymerase I and other DNA and/or RNA exonuclease domains.
Lymphoma, Non-Hodgkin
Frequent loss of BTG1 activity and impaired interactions with the Caf1 subunit of the Ccr4-Not deadenylase in non-Hodgkin lymphoma.
Malaria
CCR4-Associated Factor-1 Coordinates Expression of Plasmodium falciparum Egress and Invasion Proteins.
Melanoma
Whole exome sequencing identifies a recurrent RQCD1 P131L mutation in cutaneous melanoma.
Neoplasm Metastasis
CCR4-NOT2 Promotes the Differentiation and Lipogenesis of 3T3-L1 Adipocytes via Upregulation of PPARx03B3;, CEBP? and Inhibition of P-GSK3?/? and ?-Catenin.
Neoplasm Metastasis
Lack of effective translational regulation of PLD expression and exosome biogenesis in triple-negative breast cancer cells.
Neoplasm Metastasis
Post-transcriptional Control of Tumor Cell Autonomous Metastatic Potential by CCR4-NOT Deadenylase CNOT7.
Neoplasms
A feedback mechanism between PLD and deadenylase PARN for the shortening of eukaryotic poly(A) mRNA tails that is deregulated in cancer cells.
Neoplasms
Alterations of deadenylase expression in acute leukemias: evidence for poly(a)-specific ribonuclease as a potential biomarker.
Neoplasms
CNOT2 promotes proliferation and angiogenesis via VEGF signaling in MDA-MB-231 breast cancer cells.
Neoplasms
CNOT3 targets negative cell cycle regulators in non-small cell lung cancer development.
Neoplasms
Depletion of poly(A)-specific ribonuclease (PARN) inhibits proliferation of human gastric cancer cells by blocking cell cycle progression.
Neoplasms
Human Ccr4 and Caf1 Deadenylases Regulate Proliferation and Tumorigenicity of Human Gastric Cancer Cells via Modulating Cell Cycle Progression.
Neoplasms
Human Ccr4-Not complex is a ligand-dependent repressor of nuclear receptor-mediated transcription.
Neoplasms
Increased sensitivity and accuracy of a single-stranded DNA splint-mediated ligation assay (sPAT) reveals poly(A) tail length dynamics of developmentally regulated mRNAs.
Neoplasms
Lack of effective translational regulation of PLD expression and exosome biogenesis in triple-negative breast cancer cells.
Neoplasms
Modulation of Poly(A)-specific Ribonuclease (PARN): current knowledge and perspectives.
Neoplasms
Nuclear deadenylation/polyadenylation factors regulate 3' processing in response to DNA damage.
Neoplasms
Nuclear Tau, p53 and Pin1 Regulate PARN-Mediated Deadenylation and Gene Expression.
Neoplasms
PAPD5-mediated 3' adenylation and subsequent degradation of miR-21 is disrupted in proliferative disease.
Neoplasms
Poly(A)-specific ribonuclease and Nocturnin in squamous cell lung cancer: prognostic value and impact on gene expression.
Neoplasms
Post-transcriptional Control of Tumor Cell Autonomous Metastatic Potential by CCR4-NOT Deadenylase CNOT7.
Neoplasms
The CCR4-NOT complex is a tumor suppressor in Drosophila melanogaster eye cancer models.
Neoplasms
The proofreading domain of Escherichia coli DNA polymerase I and other DNA and/or RNA exonuclease domains.
Neoplasms
Whole exome sequencing identifies a recurrent RQCD1 P131L mutation in cutaneous melanoma.
Nervous System Diseases
Nuclear Tau, p53 and Pin1 Regulate PARN-Mediated Deadenylation and Gene Expression.
Neurologic Manifestations
Bone marrow failure and developmental delay caused by mutations in poly(A)-specific ribonuclease (PARN).
Obesity
Changes in poly(A) tail length dynamics from the loss of the circadian deadenylase Nocturnin.
Obesity
Loss of Nocturnin, a circadian deadenylase, confers resistance to hepatic steatosis and diet-induced obesity.
poly(a)-specific ribonuclease deficiency
Impaired telomere integrity and rRNA biogenesis in PARN-deficient patients and knock-out models.
poly(a)-specific ribonuclease deficiency
PARN modulates Y RNA stability, 3' end formation and its modification.
poly(a)-specific ribonuclease deficiency
Poly(A)-specific ribonuclease (PARN) mediates 3'-end maturation of the telomerase RNA component.
poly(a)-specific ribonuclease deficiency
Poly(A)-specific ribonuclease deficiency impacts telomere biology and causes dyskeratosis congenita.
poly(a)-specific ribonuclease deficiency
The RNase PARN Controls the Levels of Specific miRNAs that Contribute to p53 Regulation.
Precursor Cell Lymphoblastic Leukemia-Lymphoma
CNOT3 targets negative cell cycle regulators in non-small cell lung cancer development.
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Deletions of the long arm of chromosome 5 define subgroups of T-cell acute lymphoblastic leukemia.
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
CNOT3 targets negative cell cycle regulators in non-small cell lung cancer development.
Pulmonary Fibrosis
Cell Type-Specific Quantification of Telomere Length and DNA Double-Strand Breaks in Individual Lung Cells by Fluorescence In Situ Hybridization and Fluorescent Immunohistochemistry.
Pulmonary Fibrosis
Exome sequencing links mutations in PARN and RTEL1 with familial pulmonary fibrosis and telomere shortening.
Pulmonary Fibrosis
Poly(A)-specific ribonuclease is a nuclear ribosome biogenesis factor involved in human 18S rRNA maturation.
Pulmonary Fibrosis
Rare Genetic Variants in PARN are Associated with Pulmonary Fibrosis in Families.
Pulmonary Fibrosis
Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive.
Pulmonary Fibrosis
[A rare familial form of idiopathic pulmonary fibrosis with Poly(A)-specific ribonuclease (PARN) mutation].
rna-directed dna polymerase deficiency
Inhibition of telomerase RNA decay rescues telomerase deficiency caused by dyskerin or PARN defects.
rna-directed dna polymerase deficiency
Posttranscriptional manipulation of TERC reverses molecular hallmarks of telomere disease.
Sepsis
[Biological properties of opportunistic enterobacteria isolated from the blood of patients]
Starvation
Serum-deprivation stimulates cap-binding by PARN at the expense of eIF4E, consistent with the observed decrease in mRNA stability.
Starvation
The Recovery from Sulfur Starvation Is Independent from the mRNA Degradation Initiation Enzyme PARN in Arabidopsis.
Stomach Neoplasms
Depletion of poly(A)-specific ribonuclease (PARN) inhibits proliferation of human gastric cancer cells by blocking cell cycle progression.
Tauopathies
Distinct Poly(A) nucleases have differential impact on sut-2 dependent tauopathy phenotypes.
Tuberculosis
Structure and Function of RNase AS: A Novel Virulence Factor From Mycobacterium tuberculosis.
Virus Diseases
Resistance of vaccinia virus to interferons: modulation of the 2-5A system in interferon-treated, vaccinia virus infected cells.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
model of cooperative ligand binding by PARN dimer, binding kinetics, dissociation constants, and thermodynamics, detailed overview
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.65
Poly(A)
residues 1-446 with the deletion of the R3H domain, pH 7.0, temperature not specified in the publication
1.1
Poly(A)
residues 1-520 with the deletion of the R3H domain, pH 7.0, temperature not specified in the publication
5.6
Poly(A)
N-terminal fragment residues 1-446, pH 7.0, temperature not specified in the publication
7.6
Poly(A)
N-terminal fragment residues 1-520, pH 7.0, temperature not specified in the publication
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.645
1-(3',4'-dideoxy-3'-fluoro-beta-D-glucopyranosyl) cytosine
at pH 7.0, 30°C
0.21
1-(3',4'-dideoxy-3'-fluoro-beta-D-glucopyranosyl)-N4-benzoyl cytosine
at pH 7.0, 30°C
0.51
9-(3',4'-dideoxy-3'-fluoro-beta-D-glucopyranosyl)-N6-benzoyl adenine
at pH 7.0, 30°C
0.098
poly[2'-O-(2,4-dinitrophenyl)]poly-(A)
pH not specified in the publication, temperature not specified in the publication
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0017
1-hydroxy-3-(3-methylbutyl)-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0093
1-hydroxy-3-methyl-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0099
1-hydroxy-3-nonyl-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0048
1-hydroxy-3-pentyl-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0087
1-hydroxy-3-[(morpholin-4-yl)methyl]-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0133
1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0021
1-hydroxy-7-(2-phenylethyl)-3-(3-phenylpropyl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0106
1-hydroxy-7-(phenoxymethyl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.004
1-hydroxy-7-[(pyridin-2-yl)methyl]-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0036
1-hydroxy-7-[(thiophen-2-yl)methyl]-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0145
3-benzyl-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0207
3-decyl-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0295
3-dodecyl-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0122
3-ethyl-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0282
3-hydroxy-6,7,8,9-tetrahydropyrido[2,1-f]purine-2,4(1H,3H)-dione
Homo sapiens
pH and temperature not specified in the publication
0.00059 - 0.0239
3-[2-(dimethylamino)ethyl]-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
0.0151
6-hydroxy-1-(2-phenylethyl)-1,4-dihydro-5H-imidazo[4,5-b]pyridin-5-one
Homo sapiens
pH and temperature not specified in the publication
0.0206
7-(2-butoxyethyl)-1-hydroxy-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0015
7-benzyl-1-hydroxy-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
1
7-benzyl-1-[(prop-2-en-1-yl)oxy]-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
above, pH and temperature not specified in the publication
1
7-benzyl-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
above, pH and temperature not specified in the publication
0.0386
NSC-104148
Homo sapiens
pH and temperature not specified in the publication
0.0287
NSC-116567
Homo sapiens
pH and temperature not specified in the publication
0.525
NSC-193557
Homo sapiens
pH and temperature not specified in the publication
0.251
NSC-85703
Homo sapiens
pH and temperature not specified in the publication
0.0228
NSC-86353
Homo sapiens
pH and temperature not specified in the publication
0.0106
1-hydroxy-7-(pyridin-2-yl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.119
1-hydroxy-7-(pyridin-2-yl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0066
1-hydroxy-7-(pyridin-3-yl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.125
1-hydroxy-7-(pyridin-3-yl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0233
1-hydroxy-7-(pyridin-4-yl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.245
1-hydroxy-7-(pyridin-4-yl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0104
1-hydroxy-7-phenyl-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.0841
1-hydroxy-7-phenyl-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
0.00059
3-[2-(dimethylamino)ethyl]-1-hydroxy-7-(2-phenylethyl)-3,7-dihydro-1H-purine-2,6-dione
Homo sapiens
pH and temperature not specified in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
Vmax value is 0.30 micromol/min/micromol for the full-length enzyme at 25 mM K+
additional information
-
Vmax value is 0.36 micromol/min/micromol for the full-length enzyme at 50 mM K+
additional information
-
Vmax value is 0.42 micromol/min/micromol for the full-length enzyme at 100 mM K+
additional information
-
Vmax value is 0.42 micromol/min/micromol for the full-length enzyme at 200 mM K+
additional information
the Kd value of the wild type PARN-RNA-recognition motif enzyme for 7-methylguanosine triphosphate is 6.94 microM
additional information
Kd value of 45 microM for the interaction between PARN RNA-recognition motif and 7-methylguanosine
additional information
-
Kd value of 45 microM for the interaction between PARN RNA-recognition motif and 7-methylguanosine
additional information
10-mer poly(A) oligonucöleotide can not bind to the cap-binding site on PARN RNA-recognition motif
additional information
-
10-mer poly(A) oligonucöleotide can not bind to the cap-binding site on PARN RNA-recognition motif
additional information
PARN RRM has stronger affinity for the 7-methylguanosine than for the GpppG and GpppA cap analogs
additional information
-
PARN RRM has stronger affinity for the 7-methylguanosine than for the GpppG and GpppA cap analogs
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.4 - 10.5
-
pH 8.4: about 25% of maximum activity, pH 10.5: about 15% of maximum activity
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
37
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
(L.) Heynh. ecotypes Columbia (Col), Landsberg erecta (Ler), wassilewskija (Ws) and Nossen (Nos)
Uniprot
brenda
-
Uniprot
brenda
catalytic subunit hPAN2, regulatory subunit hPAN3: Q76E13; catalytic subunit hPAN2, regulatory subunit hPAN3
Swissprot
brenda
enzyme contains both RNA and single-stranded DNA 3-5-exonuclease activities
-
-
brenda
strains L40 and yAS1255, a pab1DELTA strain, and a pan3DELTA strain yME43
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
poly(A)-specific ribonuclease (PARN) is upregulated in gastric tumor tissues and gastric cancer cell lines MKN28 and AGS, determination of the expression level of PARN in human gastric cancer cells and tissues by quantitative real-time PCR expression analysis
brenda
the expression of deadenylase PARN is differentially expressed in SCC clinical samples. PARN overexpression correlates with younger patient age. Kaplan-Meier analysis suggests that increased levels of PARN correlates with significantly increased survival
brenda
expression of nocturnin mRNA is confined to the clock-containing photoreceptor cell layer within the retina
brenda
the expression of deadenylase PARN is differentially expressed in SCC clinical samples. PARN overexpression correlates with younger patient age. Kaplan-Meier analysis suggests that increased levels of PARN correlates with significantly increased survival
brenda
additional information
differentiated cells express PNLDC1 only after demethylation
brenda
differentiated cells express PNLDC1 only after demethylation
brenda
additional information
PNLDC1 is present in stem and germ cells and fades during embryogenesis and early differentiation. Pnldc1 is highly expressed in mouse embryonic stem cells (E14) and testes, whereas expression in skin, late embryos and ovaries is almost undetectable (albeit slightly higher in ovaries than other organs)
brenda
additional information
-
PNLDC1 is present in stem and germ cells and fades during embryogenesis and early differentiation. Pnldc1 is highly expressed in mouse embryonic stem cells (E14) and testes, whereas expression in skin, late embryos and ovaries is almost undetectable (albeit slightly higher in ovaries than other organs)
brenda
additional information
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Trypanosomatids possess three different PARN genes, PARN-1, -2, and -3, each of which is expressed at the mRNA level in two life-cycle stages of the human parasite Trypanosoma brucei
brenda
additional information
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Trypanosomatids possess three different PARN genes, PARN-1, -2, and -3, each of which is expressed at the mRNA level in two life-cycle stages of the human parasite Trypanosoma brucei
-
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
PARN is encoded for by two alternative splice variants predicted to localize to the nucleus and to chloroplasts/mitochondria, respetively
brenda
residues 506-525 in HsPNLDC1-1 represent a putative transmembrane domain
brenda
additional information
nocturnin is expressed in the cytoplasm of rod and cone photoreceptor cells
brenda
PNLDC1 is localized predominantly in the endoplasmic reticulum
brenda
peripheral membrane protein bound with ER membrane via ionic interactions. The C-terminal domain contributes to the membrane-binding ability of PARN. ER-anchored PARN modulates poly(A) tail length distribution of ER-associated mRNAs but does not affect global translation effciency
brenda
PNLDC1 is localized predominantly in the endoplasmic reticulum
brenda
mitochondrial localizations of isoform AHG2 and poly(A) polymerase AGS1 are required for their functions in the regulation of the poly(A) tract of mitochondrial mRNA
brenda
PARN is encoded for by two alternative splice variants predicted to localize to the nucleus and to chloroplasts/mitochondria, respectively
brenda
-
citrine-fused proteins AGS1 and AHG2 are localized to mitochondria
brenda
a core motif for localization to the nucleolus is located at residues 605-616
brenda
PARN is encoded for by two alternative splice variants predicted to localize to the nucleus and to chloroplasts/mitochondria, respetively
brenda
PARN occurs in the nucleus, upstream of the final endonucleolytic cleavage by the endonuclease NOB1 in the cytoplasm
brenda
the region of reidues 523-540 is responsible for nuclear localization of PARN
brenda
additional information
PARN co-purifies with 40S subunit precursors
-
brenda
additional information
PARN, as a component of the pre-40S particle, pulls down with the pre-ribosome factor LTV1 or Bystin. PARN is a constitutive component of the Bystin-associated pre-40S particle
-
brenda
additional information
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PARN, as a component of the pre-40S particle, pulls down with the pre-ribosome factor LTV1 or Bystin. PARN is a constitutive component of the Bystin-associated pre-40S particle
-
brenda
additional information
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Pab1p contains a non-essential leucine-rich nuclear export signal and shuttles in an Xpo1/Gsp-1-dependent manner between the nucleus and the cytoplasm
-
brenda
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
PARN is a member of the DEDD family of 3'-to-5' exonucleases with a marked nucleotide preference towards A
malfunction
metabolism
physiological function
additional information
malfunction
depletion of poly(A)-specific ribonuclease (PARN) inhibits proliferation of human gastric cancer cells by blocking cell cycle progression. PARN depletion leads to cell cycle arrest by upregulating p21 expression, stabilizes the p21 mRNA (one of the key regulators in cell growth and survival), and promotes cell death, but does not affect the formation of RNA granules
malfunction
AGO-APP from parental or PARN knockout cells enrich the miRNAs to a similar extent, without altering the overall length distribution of the miRNA isoforms, suggesting that PARN-mediated trimming does not affect the interaction of miRNAs with AGO proteins
malfunction
mutations in PARN in patients with haematological and neurological manifestations. Large monoallelic deletions in PARN in four patients with developmental delay or mental illness. One patient in particular has a severe neurological phenotype, central hypomyelination and bone marrow failure. This patient has an additional missense mutation on the non-deleted allele and severely reduced PARN protein and deadenylation activity. Cells from this patient have impaired oligoadenylation of specific H/ACA box small nucleolar RNAs. Importantly, PARN-deficient patient cells manifest short telomeres and an aberrant ribosome profile similar to those described in some variants of dyskeratosis congenita. Knocking down PARN in human marrow cells impaires haematopoiesis. Biallelic mutations in PARN results in severely reduced protein level. PARN-deficient patient cells manifest PARN-associated defects in snoRNA and scaRNA trimming and aberrant ribosome profile. Phenotypes, detailed overview
malfunction
mutations in the PARN gene (encoding poly(A)-specific ribonuclease) cause telomere diseases including familial idiopathic pulmonary fibrosis and dyskeratosis congenita. PARN deficiency impairs telomere maintenance. Mechanism linking PARN mutations to telomere diseases, phenotype analysis, overview
malfunction
knocking down ribosome biogenesis factors (RBFs) involved in the large subunit pathway (LSG1 and eIF6) has no effect on PARN localization. Co-depletion of PARN and NOB1 yields a much stronger accumulation of 18S-EFL species than the sole knockdown of PARN. This suggests that NOB1 can also cleave untrimmed 18S-E pre-rRNAs, albeit less efficiently. In accordance with this assumption, overexpression of NOB1 in PARN-depleted cells leads to a decreased amount of 18S-EFL pre-rRNA
malfunction
knockdown of PARN or exogenous expression of an enzyme-dead PARN mutant (D28A) accumulates 18S-E in both the cytoplasm and nucleus. Expression of D28A accumulates 18S-E in Bystin-associated pre-40S particles. RNase H-based fragmentation analysis and 3'-sequence analysis of 18S-E species present in cells expressing wild-type PARN or D28A, overview
malfunction
Noc knock-out (Noc-/-) mice exhibit no obvious abnormalities in development or reproduction, however, they exhibit striking metabolic phenotypes when fed a High-Fat Diet (HFD). This diet causes wild-type mice to become obese, but the Noc-/- mice remain lean although they do not exhibit increased activity or reduced food intake
malfunction
mice lacking the Noc gene display resistance to diet-induced obesity and hepatic steatosis, due in part to reduced lipid trafficking in the small intestine
malfunction
natural mutation Y91C leads to reduced deadenylase activity, natural mutation I274* leads to depletion of transcript level. Increased adenylation of telomerase RNA, hTR, and certain snoRNAs, and impaired rRNA maturation are observed in cells derived from a severely affected biallelic carrier, but not in the other, less affected biallelic carrier, who has less severely shortened telomeres, nor in the monoallelic carriers who are unaffected and have telomeres ranging from the 1st to the 50th percentiles
metabolism
3' ends of metazoan microRNAs (miRNAs) are initially defined by the RNase III enzymes during maturation, but subsequently experience extensive modifications by several enzymatic activities. For example, terminal nucleotidyltransferases (TENTs) elongate miRNAs by adding one or a few nucleotides to their 3' ends, which occasionally leads to differential regulation of miRNA stability or function. Poly(A)-specific ribonuclease (PARN) forms the 3' ends of miRNAs in human cells
metabolism
the expression of several deadenylases is altered in squamous cell lung cancer, SCC. Quantitative real-time PCR shows that four deadenylases, PARN, CNOT6, CNOT7 and NOC, are differentially expressed in SCC clinical samples. PARN overexpression correlates with younger patient age and CNOT6 overexpression with non-metastatic tumors. Kaplan-Meier analysis suggests that increased levels of PARN and NOC correlate with significantly increased survival. The gene expression deregulation is functionally enriched for gene ontologies related to cell adhesion, cell junction, muscle contraction and metabolism
metabolism
the enzyme plays a role in mRNA catabolism and in exonucleolytic trimming of 18S-E pre-rRNA
physiological function
-
PARN-1 is an active deadenylase, PARN-1 is nonessential for parasite viability
physiological function
poly(A)-specific ribonuclease is involved in the mRNA decay regulation by specifically catalyzing the shortening of the 3'-end poly(A) tail
physiological function
isoform AHG2 directly regulates the poly(A) tract of mitochondrial mRNA in conjunction with a bacterial-type poly(A) polymerase, AGS1. A ribonuclease-deficient mutant accumulates polyadenylated mitochondrial mRNA and shows defects in mitochondrial protein complex levels. Mutations of AGS1 suppress the AHG2 mutant phenotype. Mitochondrial localizations of AHG2 and AGS1 are required for their functions in the regulation of the poly(A) tract of mitochondrial mRNA
physiological function
the R3H domain has the ability to bind various oligonucleotides at the micromolar level with no oligo(A) specificity. The removal of the R3H domain dissociates poly(A)-specific ribonuclease into monomers, which still possess the RNA-binding ability and catalytic functions. The removal of the R3H domain does not affect the catalytic pattern of poly(A)-specific ribonuclease. Both R3H domain and RNA-recognition motif domain RRM may be essential for the high affinity of long poly(A) substrate, but the R3H domain does not contribute to the substrate recognition. Compared to the RRM domain, the R3H domain plays a more important role in the structural integrity of the dimeric poly(A)-specific ribonuclease
physiological function
infection of zebra fish with a RNase AS deletion mutant strain is reduced to 4.7% of wild-type. The knockout can be complemented by Mycobacterium tuberculosis gene rv2179c encoding a 3'-5' exoribonuclease
physiological function
the action of PARN strongly relies on protein expression profiles of the cells, which leads to heterogeneity in the stability of PARN-targeted mRNAs
physiological function
in eukaryotic cells, cytoplasmic mRNA is characterized by the presence of a 3' poly(A) tail. The median length of the tail varies from 27 to 28 nucleotides in yeast to 60-100 nucleotides in mammalian cells.The tail is important for the control of gene expression, enzymatic shortening of the poly(A) tail (deadenylation) can initiate mRNA degradation and repress translation. An important enzyme involved in cytoplasmic deadenylation is the multi-component Ccr4-Not complex. In addition to six noncatalytic subunits, the complex contains two subunits with ribonuclease activity: both Caf1 and Ccr4 display Mg2+-dependent 3'-'-5' exoribonuclease activity with a preference for poly(A). While the enzymatic activity of Caf1 is associated with an RNAse D/DEDD (Asp-Glu-Asp-Asp) domain, the enzymatic activity of Ccr4 is provided by an EEP (endonuclease-exonuclease-phosphatase) domain
physiological function
poly(A)-specific ribonuclease (PARN) forms the 3' ends of miRNAs in human cells. PARN digests the 3' extensions of miRNAs that are derived from the genome or attached by TENTs, thereby effectively reducing the length of miRNAs. PARN-mediated shortening has little impact on miRNA stability, suggesting that this process likely operates to finalize miRNA maturation, rather than to initiate miRNA decay. PARN-mediated shortening is pervasive across most miRNAs and appears to be a conserved mechanism contributing to the 3' end formation of vertebrate miRNAs. PARN has the unique ability to interact with the 7-methylguanosine cap of mRNAs. Enzyme PARN functions as a trimmer to digest the genome-encoded 3' extensions of miRNAs, and PARN shapes the 3' ends of microRNAs as a de-tailor to erase or reduce the size of untemplated nucleotide additions. PARN emerges as a miR-362-5p trimmer in vitro and in vivo, and as general miRNA trimmer
physiological function
deadenylation regulates RNA function and fate. Poly(A)-specific ribonuclease (PARN) is a deadenylase that processes mRNAs and non-coding RNA
physiological function
poly(A)-specific ribonuclease (PARN) mediates 3'-end maturation of the telomerase RNA component. PARN is required for removal of post-transcriptionally acquired oligo(A) tails that target nuclear RNAs for degradation. Diminished TERC levels and the increased proportion of oligo(A) forms of TERC are normalized by restoring PARN, which is limiting for TERC maturation in cells. Role for PARN in the biogenesis of TERC. TERC serves as the RNA template and scaffold for the telomerxadase reverse-transcriptase holoenzyme
physiological function
PNLDC1 is a deadenylase that is excluded from the nucleus and most likely, its function occurs mainly in the endoplasmic reticulum
physiological function
PNLDC1 is a deadenylase that is excluded from the nucleus and most likely, its function occurs mainly in the endoplasmic reticulum. Pnldc1 is present in early mouse development
physiological function
poly(A)-specific ribonuclease is a nuclear ribosome biogenesis factor involved in human 18S rRNA maturation. The enzyme supports the processing of different types of non-coding RNAs including telomerase RNA. PARN is part of the enzymatic machinery that matures the human 18S ribosomal RNA (rRNA). PARN is required for 40S ribosomal subunit production. Function of PARN in exonucleolytic trimming of 18S-E pre-rRNA. A number of nucleolar 40S-specific ribosome biogenesis factors (RBFs), including ENP1, DIM2, RRP12, LTV1 and TSR1, accompany pre-40S particles from the nucleolus via the nucleoplasm to the cytosol. Like shuttling nucleolar RBFs, PARN redistributes from the nucleolus to the nucleoplasm upon inhibition of pre-40S particle export by leptomycin B. PARN is coupled to a poly(A) polymerase for processing of the 18S-E pre-rRNA. PARN is primarily involved in pre-rRNA processing, not in quality control
physiological function
poly(A)-specific ribonuclease regulates the processing of small-subunit rRNAs in human cells, poly(A)-specific ribonuclease (PARN) participates in steps leading to 18S-E maturation in human cells. Ribosome biogenesis occurs successively in the nucleolus, nucleoplasm, and cytoplasm. Maturation of the ribosomal small subunit is completed in the cytoplasm by incorporation of a particular class of ribosomal proteins and final cleavage of 18S-E pre-rRNA (18S-E). The enzymatic activity of PARN is necessary for the release of 18S-E from Bystin-associated pre-40S particles. PARN degrades the extended regions encompassing nucleotides 5-44 at the 3' end of mature 18S rRNA
physiological function
poly(A)-specific ribonuclease (PARN) catalyzes the degradation of mRNA poly(A) tail to regulate translation efficiency and mRNA decay in higher eukaryotic cells. PARN has the unique properties of 5'-cap-binding ability, high activity, allosteric regulation, processive catalysis and highly regulated deadenylation in the cells
physiological function
while nocturnin is rhythmically expressed in the cytoplasm of the retinal photoreceptor cells, the only other described vertebrate deadenylase, PARN, is constitutively present in most retinal cells, including the photoreceptors. The distinct spatial and temporal expression of nocturnin and PARN suggests that there may be specific mRNA targets of each deadenylase. Since deadenylation regulates mRNA decay and/or translational silencing, it is proposed that nocturnin deadenylates clock-related transcripts in a novel mechanism for posttranscriptional regulation in the circadian clock or its outputs
physiological function
while nocturnin is rhythmically expressed in the cytoplasm of the retinal photoreceptor cells, the only other described vertebrate deadenylase, PARN, is constitutively present in most retinal cells, including the photoreceptors. The distinct spatial and temporal expression of nocturnin and PARN suggests that there may be specific mRNA targets of each deadenylase
physiological function
PARN, nocturnin and Angel are three of the multiple deadenylases that have been described in eukaryotic cells. While each of these enzymes appears to target poly(A) tails for shortening and influence RNA gene expression levels and quality control, the enzymes differ in terms of enzymatic mechanisms, regulation and biological impact. Nocturnin functions in adipogenesis and lipid metabolism
physiological function
PARN, nocturnin and Angel are three of the multiple deadenylases that have been described in eukaryotic cells. While each of these enzymes appears to target poly(A) tails for shortening and influence RNA gene expression levels and quality control, the enzymes differ in terms of enzymatic mechanisms, regulation and biological impact. PARN plays a role in early development, DNA damage and possibly cancer
physiological function
PARN, nocturnin and Angel are three of the multiple deadenylases that have been described in eukaryotic cells. While each of these enzymes appears to target poly(A) tails for shortening and influence RNA gene expression levels and quality control, the enzymes differ in terms of enzymatic mechanisms, regulation and biological impact. PARN plays a role in early development, DNA damage and possibly cancer
physiological function
the enzyme is involved in the removal of polyA tails from mRNAs. Noc is a potential key post-transcriptional mediator in the circadian control of many metabolic processes. It appears to play important roles in other tissues and has been implicated in lipid metabolism, adipogenesis, glucose homeostasis, inflammation and osteogenesis
physiological function
under normal conditions, the nucleolus-residing PARN recruits cap-binding protein CBP80 into the nucleoli to repress its deadenylase activity, while DNA damage-induced phosphorylation of PARN-S557 expells CBP80 from the nucleoli to discharge activity inhibition and attracts nucleoplasm-located CstF-50 into the nucleoli to activate deadenylation
physiological function
-
isoform AHG2 is essential and functionally interacts with AGS1. Overexpression of AGS1 and the reduced expression of AHG2 cause an accumulation of polyadenylated Cox1 mRNA. Loss-of-function mutants of AHG2 or AGS1 exhibit weak growth retardation phenotypes under normal growth conditions. The fresh weights of the thallus of the AGS1 mutants are about 65% of that of wild-type
physiological function
the ER-anchored PARN triggers the degradation of a small subset of ER-enriched transcripts. The ER-anchored PARN modulates the translation of its targets by redistributing ribosomes to heavy polysomes. During DNA damage response, MK2 phosphorylates PARN residue Ser557 to modulate PARN translocation from the ER to cytosol. The ER-anchored PARN modulates DNA damage response and thereby cell viability by promoting the decay of ER-associated MDM2 transcripts with low ribosome occupancy. Ser557 phosphorylation modulates the ER localization of PARN to respond to DNA damage response
physiological function
the degradation of sulfur starvation-induced genes during the recovery from starvation is independent of PARN
physiological function
after PARN gene knockout, the apoptosis rate of esophageal cancer cells is significantly increased, the growth and proliferation of tumor cells are significantly inhibited, and the invasion and migration ability of tumor cells are significantly decreased
physiological function
-
PARN-1 is an active deadenylase, PARN-1 is nonessential for parasite viability
-
additional information
alterations in the active site structure by metal binding or mutations might lead to a global conformational change of the enzyme PARN molecule
additional information
-
the active site of PARN per se harbors specificity for recognition of adenosine
additional information
in the structure of PF2046 complexed with an oligonucleotide of four thymidine nucleotides (dT4), PF2046 accommodates dT4 tightly in a groove and imposes steric hindrance on dT4 mainly by residue Phe220 such that dT4 assumes the A-form. As poly-dA prefer B-form due to the stereochemical restrictions, the A-form ssDNA binding by PF2046 disfavors the processing of poly-dA. Phe220 variants display reduced activity toward poly-dA and the A-form appears to be a prerequisite for the processing by PF2046
additional information
poly(A)-specific ribonuclease (PARN) is a dimeric exoribonuclease that efficiently degrades mRNA 3' poly(A) tails while also simultaneously interacting with the mRNA 5' cap. The mRNA 5' cap structure plays a pivotal role in coordination of eukaryotic translation and mRNA degradation. Molecular recognition of mRNA 5' cap by 3' poly(A)-specific ribonuclease (PARN) differs from interactions known for other cap-binding proteins: 1. the auxiliary biological function of 5' cap binding by the 3' degrading enzyme is accomplished by negative cooperativity of PARN dimer subunits, 2. non-coulombic interactions are major factors in the complex formation, and 3. PARN has versatile activity toward alternative forms of the cap. These characteristics contribute to stabilization of the PARN-cap complex needed for the deadenylation processivity. Fluorescence and NMR spectroscopic analysis. Model of cooperative ligand binding by PARN dimer. Enzyme-ligand (cap and cap analogues) interaction analysis by surface plasmon resonance, local conformational changes of PARN upon 5' mRNA cap binding, small increase in the beta-strand and coil contributions and complex formation in the vicinity of the residues Trp475 and Asp478. PARN seems to recognize the 5' cap in a simple fashion by virtue of the single-sided stacking that is unique among cap-binding proteins
additional information
isozyme PARN contains a characteristic nuclear localisation signal (NLS, residues 520-540), a carboxy terminal domain (CTD, 540-639) which are not conserved in PNLDC1 and additional regions, which are absent in PNLDC1. The RRM domain of PARN (445-520) is partially conserved in PNLDC1. HsPNLDC1 active site model, overview. RNA-binding sites of HsPNLDC1, comparison to HsPARN revealing similarities in the spatial arrangement of the catalytic DEDDh-motif and other RNA-interacting residues
additional information
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isozyme PARN contains a characteristic nuclear localisation signal (NLS, residues 520-540), a carboxy terminal domain (CTD, 540-639) which are not conserved in PNLDC1 and additional regions, which are absent in PNLDC1. The RRM domain of PARN (445-520) is partially conserved in PNLDC1. HsPNLDC1 active site model, overview. RNA-binding sites of HsPNLDC1, comparison to HsPARN revealing similarities in the spatial arrangement of the catalytic DEDDh-motif and other RNA-interacting residues
additional information
the C-terminal domain (CTD) prevents PARN from thermal inactivation but promotes thermal aggregation to initiate at a temperature much lower than that required for inactivation and unfolding
additional information
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in the structure of PF2046 complexed with an oligonucleotide of four thymidine nucleotides (dT4), PF2046 accommodates dT4 tightly in a groove and imposes steric hindrance on dT4 mainly by residue Phe220 such that dT4 assumes the A-form. As poly-dA prefer B-form due to the stereochemical restrictions, the A-form ssDNA binding by PF2046 disfavors the processing of poly-dA. Phe220 variants display reduced activity toward poly-dA and the A-form appears to be a prerequisite for the processing by PF2046
-
additional information
-
in the structure of PF2046 complexed with an oligonucleotide of four thymidine nucleotides (dT4), PF2046 accommodates dT4 tightly in a groove and imposes steric hindrance on dT4 mainly by residue Phe220 such that dT4 assumes the A-form. As poly-dA prefer B-form due to the stereochemical restrictions, the A-form ssDNA binding by PF2046 disfavors the processing of poly-dA. Phe220 variants display reduced activity toward poly-dA and the A-form appears to be a prerequisite for the processing by PF2046
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additional information
-
in the structure of PF2046 complexed with an oligonucleotide of four thymidine nucleotides (dT4), PF2046 accommodates dT4 tightly in a groove and imposes steric hindrance on dT4 mainly by residue Phe220 such that dT4 assumes the A-form. As poly-dA prefer B-form due to the stereochemical restrictions, the A-form ssDNA binding by PF2046 disfavors the processing of poly-dA. Phe220 variants display reduced activity toward poly-dA and the A-form appears to be a prerequisite for the processing by PF2046
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Show AA Sequence and Transmembrane Helices (18546 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
135007
x * 135007, catalytic subunit hPAN2, + x * 75886, regulatory subunit hPAN3, calculated from amino acid sequence
161000
54000
74000
75886
x * 135007, catalytic subunit hPAN2, + x * 75886, regulatory subunit hPAN3, calculated from amino acid sequence
161000
-
135000 polypeptide is not required for poly(A)-ribonuclease activity
74000
-
3 * 74000, SDS-PAGE, a 54000 Da polypeptide fragment is responsible for activity
74000
4 * 74000, calculated. Poly(A)-specific ribonuclease PARN can self-associate into tetramer and high-order oligomers both in vitro and in living cells. PARN oligomerization is triggered by the R3H domain,which leads to the solvent-exposed Trp219 fluorophore to become buried in a solvent-inaccessible microenvironment. The RRM and C-terminal domains are involved in modulating the dissociation rate of the tetrameric PARN. Tetramerization does not affect the catalytic behavior of the full-length PARN and truncated enzymes containing the RRM domain. Tetramerization significantly enhances the catalytic activity and processivity of the truncated form with the removal of the RRM and C-terminal domains
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
monomer
gel filtration experiments show that the PARN-RNA-recognition motif domain predominantly exists as a monomer, but about 5% elute at a volume corresponding to a homodimer
tetramer
4 * 74000, calculated. Poly(A)-specific ribonuclease PARN can self-associate into tetramer and high-order oligomers both in vitro and in living cells. PARN oligomerization is triggered by the R3H domain,which leads to the solvent-exposed Trp219 fluorophore to become buried in a solvent-inaccessible microenvironment. The RRM and C-terminal domains are involved in modulating the dissociation rate of the tetrameric PARN. Tetramerization does not affect the catalytic behavior of the full-length PARN and truncated enzymes containing the RRM domain. Tetramerization significantly enhances the catalytic activity and processivity of the truncated form with the removal of the RRM and C-terminal domains
trimer
-
3 * 74000, SDS-PAGE, a 54000 Da polypeptide fragment is responsible for activity
additional information
?
x * 135007, catalytic subunit hPAN2, + x * 75886, regulatory subunit hPAN3, calculated from amino acid sequence
?
x * 61300, isozyme 1 of HsPNLDC1, sequence calculation, x * 60100, isozyme 2 of HsPNLDC1, sequence calculation
homodimer
gel filtration experiments show that the PARN-RNA-recognition motif domain predominantly exists as a monomer, but about 5% elute at a volume corresponding to a homodimer
homodimer
PARN mainly exists as a homodimer in solutions, while it can also associate into larger oligomers via its R3H domain
additional information
the human enzyme is composed of at least three functional domains, i.e. the catalytic nuclease domain and two RNA binding domains, the R3H and the RNA recognition motif, respectively, detailed analysis of the global architecture of the human enzyme and dimensions of the full-length protein at subnanometer resolution, by atomic force microscopy imaging, overview
additional information
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the human enzyme is composed of at least three functional domains, i.e. the catalytic nuclease domain and two RNA binding domains, the R3H and the RNA recognition motif, respectively, detailed analysis of the global architecture of the human enzyme and dimensions of the full-length protein at subnanometer resolution, by atomic force microscopy imaging, overview
additional information
the full length PARN enzyme contains three well-defined domains: the catalytic domain, the R3H domain, and the RNA-recognition motif, RRM
additional information
full-length PARN is a multi-domain protein containing the catalytic nuclease domain, the R3H domain, the RRM domain and the C-terminal intrinsically unstructured domain (CTD). Impact of CTD on PARN stability and aggregatory potency, comparing the thermal inactivation and denaturation behaviors of full-length PARN with two N-terminal fragments lacking CTD. K+ induces additional regular secondary structures and enhances PARN stability against heat-induced inactivation, unfolding and aggregation. The CTD prevents PARN from thermal inactivation but promotes thermal aggregation to initiate at a temperature much lower than that required for inactivation and unfolding. Domain architecture of PARN and effects of K+ on p74, p60 and p46 secondary and tertiary structures, overview
additional information
the C-terminal domain is intrinsically disordered with loosely packed local structures/tertiary structure. The C-terminal domain is indispensable for the interaction between PARN and cap binding protein CBP80
additional information
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the enzyme requires the subunits Pan2p and Pan3p, as well as the poly(A)-binding protein Pab1p for activity
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
side-chain modification
PARN is primarily acetylated by the acetyltransferase p300 at Lys566 and deacetylated by sirtuin SIRT1. Acetylation of PARN decreases its enzymatic activity both in vitro, and in vivo. SIRT1 can regulate levels of adenylated human telomerase RNA component through PARN
phosphoprotein
-
in leukemic cells from patients with acute lymphoblastic leukemia, a significant amount of poly(A)-specific ribonuclease is phosphorylated
phosphoprotein
Ser557 phosphorylation modulates the ER localization of PARN to respond to DNA damage response
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure of the PARN-RNA-recognition motif domain (residues 445-540) with a bound 7-methylguanosine triphosphate nucleotide shows a remarkable conformational flexibility of the RNA-recognition motif domain, crystal structure is refined at a resolution of 2.1 A, protein folds into a three-stranded antiparallel beta-sheet that is flanked by one alpha-helix connecting beta-strands beta1 and beta2
in silico model for catalytic mechanism and development of a 3D pharmacophore model. Residues Arg99 and Gln109 are involved in the regulation of catalysis. The natural preference of the enzyme for poly(A) is based on favorable biophysical electrostatic and hydrophobic interactions
purified recombinant CNOT6L nuclease domain in complex with AMP and poly(A) DNA, hanging drop vapour diffusion method, 0.001 ml of protein solution, containing 15 mg/ml protein and 1 mM DTT, is mixed with 0.001 ml of reservoir solution and equilibrated over 300 ml reservoir solution, containing 0.1 M HEPES, pH 7.5, 1.1 M ammonium tartrate, and 0.2 M NDSB-201, at 16°C, X-ray diffraction structure determination and analysis at 1.94-2.44 A resolution
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enzyme PF2046 complexed with an oligonucleotide of four thymidine nucleotides (dT4), X-ray diffraction structure determination and analysis
Pop2p crystallized by the sitting drop vapour diffusion technique, to 1.4 A resolution by X-ray crystallography, crystals belong to the space group P212121, contains a fully conserved DEDDh active site
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D66A/E68A
-
site-directed mutagenesis, enzymatically inactive PARN, the mutant embryos are retarded, and culminate in an arrest at the bent-cotyledon stage, some show hyperadenylation of transcripts
D28C
-
mutants inactive in presence of Mg2+, but with restored activity in presence of soft divalent metal ions, amino acid interacts with catalytically essential metal ions
D292C
-
mutants inactive in presence of Mg2+, but with restored activity in presence of soft divalent metal ions, amino acid interacts with catalytically essential metal ions
D382C
-
mutants inactive in presence of Mg2+, but with restored activity in presence of soft divalent metal ions, amino acid interacts with catalytically essential metal ions
D28C
-
mutants inactive in presence of Mg2+, but with restored activity in presence of soft divalent metal ions, amino acid interacts with catalytically essential metal ions
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D292C
-
mutants inactive in presence of Mg2+, but with restored activity in presence of soft divalent metal ions, amino acid interacts with catalytically essential metal ions
-
D382C
-
mutants inactive in presence of Mg2+, but with restored activity in presence of soft divalent metal ions, amino acid interacts with catalytically essential metal ions
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D28A
D292A
D382A
D478A
generated by site-directed mutagenesis, Kd value for 7-methylguanosine triphosphate is 20.0 microM
E30A
F484A
-
site-directed mutagenesis, active site mutant, not expressable in Escherichia coli
H449A
site-directed mutagenesis, the mutant shows loss of the negative cooperativity between the PARN dimer subunits that is evident for the m7GpppG and m7GTP binding by the wild-type protein
K454A
generated by site-directed mutagenesis, Kd value for 7-methylguanosine triphosphate is 20.03 microM
K566R
mutation reduces PARN acetylation, the mutation increases PARN enzymatic activity
L197A
-
site-directed mutagenesis, active site mutant, not expressable in Escherichia coli
L216A
-
site-directed mutagenesis, active site mutant, not expressable in Escherichia coli
L291A
-
site-directed mutagenesis, activity and kinetics with RNA substrates compared to the wild-type enzyme
L414A
-
site-directed mutagenesis, active site mutant, not expressable in Escherichia coli
M425A
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site-directed mutagenesis, activity and kinetics with RNA substrates compared to the wild-type enzyme
N412A
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site-directed mutagenesis, active site mutant, not expressable in Escherichia coli
P365A
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site-directed mutagenesis, active site mutant, not expressable in Escherichia coli
P365A/F484A
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site-directed mutagenesis, active site mutant, not expressable in Escherichia coli
P365A/N412A/F484A
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site-directed mutagenesis, active site mutant, not expressable in Escherichia coli
S557D
phosphorylation-mimic mutation, disrupts the local structure and facilitates the binding of the C-terminal domain with the well-folded domains, no impact on PARNdeadenylase activity
T458A
generated by site-directed mutagenesis, Kd value for 7-methylguanosine triphosphate is 30.58 microM
D471A
point mutation is introduced into the cap-binding domain usin site-directed mutagenesis kit, pull-down assay shows no significant impact on the cap-binding activity of PARN
K447A
point mutation is introduced into the cap-binding domain using site-directed mutagenesis kit, pull-down assay shows no significant impact on the cap-binding activity of PARN
K450A
point mutation is introduced into the cap-binding domain using site-directed mutagenesis kit, pull-down assay shows no significant impact on the cap-binding activity of PARN
W468L
point mutation is introduced into the cap-binding domain using site-directed mutagenesis kit, mutation significantly decreases the interaction between PARN RNA-recognition motif and the cap analog, the aromatic ring of W468 is directly responsible for the cap recognition and is a functionally critical residue for the cap-binding activity of PARN RNA-recognition motif
A519V
-
site-directed mutagenesis of Pab1p, the mutant shows no resistance to 3-AT in contrast to the wild-type protein, identification of interaction residues and domains with Ppb1p, Pan2p and Pan3p
E556A
-
complete loss of activity, E556 is the key Mg2+-binding residue
G444D
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site-directed mutagenesis of Pab1p, the mutant shows no resistance to 3-AT in contrast to the wild-type protein, identification of interaction residues and domains with Ppb1p, Pan2p and Pan3p
G528D
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site-directed mutagenesis of Pab1p, the mutant shows no resistance to 3-AT in contrast to the wild-type protein, identification of interaction residues and domains with Ppb1p, Pan2p and Pan3p
R506G
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site-directed mutagenesis of Pab1p, the mutant shows no resistance to 3-AT in contrast to the wild-type protein, identification of interaction residues and domains with Ppb1p, Pan2p and Pan3p
V451A
-
site-directed mutagenesis of Pab1p, the mutant shows no resistance to 3-AT in contrast to the wild-type protein, identification of interaction residues and domains with Ppb1p, Pan2p and Pan3p
Y514C
-
site-directed mutagenesis of Pab1p, the mutant shows reduced resistance to 3-AT compared to the wild-type protein, identification of interaction residues and domains with Ppb1p, Pan2p and Pan3p
additional information
D28A
site-directed mutagenesis, structure comparison to the wild-type enzyme, the mutant shows unaltered ellipticity
D28A
site-directed mutagenesis, catalytically inactive mutant, phenotype, overview
D292A
site-directed mutagenesis, structure comparison to the wild-type enzyme, the mutant shows unaltered ellipticity
D382A
site-directed mutagenesis, structure comparison to the wild-type enzyme, the mutant shows slightly decreased ellipticity
E30A
site-directed mutagenesis, structure comparison to the wild-type enzyme, the mutant shows significantly decreased ellipticity
additional information
-
construction of embryos lacking PARN, the mutant embryos are retarded, and culminate in an arrest at the bent-cotyledon stage, some show hyperadenylation of transcripts, the phenotype cannot be rescued by expression of the wild-type enzyme in plants, loss of the enzyme affects poly(A) tail length distribution of only a select subset of embryonic transcripts
additional information
-
gene silencing by microinjection of specific iRNA, the mutant worms show no phenotype
additional information
-
removal of the R3H domain (mutant p74DR3H) leads to a dramatic decrease in the thermal stability of PARN, while removal of the RRM domain or both of the two RNA-binding domains only results in a minor decrease in PARN stability against thermal inactivation and denaturation
additional information
-
PARN(443-560/W456/W475A) mutant is severely defective in cap binding, has RNA binding properties
additional information
construction of deletion mutants, i.e. expression of the N-terminal fragment residues 1-540, the N-terminal fragment residues 1-520, the N-terminal fragment residues 1-470, the N-terminal fragment residues 1-446, residues 1-520 with the deletion of the R3H domain, residues 1-446 with the deletion of the R3H domain. N-terminal fragment residues 1-446, residues 1-520 with the deletion of the R3H domain, residues 1-446 with the deletion of the R3H domain display 30.9%, 5.9% and 2.5% of the catalytic efficiency of the N-terminal fragment residues 1-520, respectively
additional information
stable knockdown of the endogenous PARN in the gastric cancer MKN28 and AGS cells. PARN depletion significantly inhibits the proliferation of the two types of gastric cancer cells and promotes cell death, but does not significantly affect cell motility and invasion. The depletion of PARN arrests the gastric cancer cells at the G0/G1 phase by upregulating the expression levels of p53 and p21 but not p27. The mRNA stability of p53 is unaffected by PARN-knockdown in both types of cells. A significant stabilizing effect of PARN-depletion on p21 mRNA is observed in the AGS cells but not in the MKN28 cells
additional information
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stable knockdown of the endogenous PARN in the gastric cancer MKN28 and AGS cells. PARN depletion significantly inhibits the proliferation of the two types of gastric cancer cells and promotes cell death, but does not significantly affect cell motility and invasion. The depletion of PARN arrests the gastric cancer cells at the G0/G1 phase by upregulating the expression levels of p53 and p21 but not p27. The mRNA stability of p53 is unaffected by PARN-knockdown in both types of cells. A significant stabilizing effect of PARN-depletion on p21 mRNA is observed in the AGS cells but not in the MKN28 cells
additional information
generation of PARN knockout cells by CRISPR/Cas9-mediated gene knockout. Complementation of PARN activity restores the normal isoform ratio of miR-362-5p in HEK-293T cells
additional information
-
growth of cells transformed with mutant constructs, overview
additional information
-
ccr4delta mutant strain, residual deadenylation is solely due to the Pan2p/Pan3p complex, the MFA2pG mRNA in the nonstressed ccr4delta cells is stabilized 2fold compared to the wild-type strain, difference in deadenylation rates with and without stress in the ccr4D strain is not as severe as in wild-type cells
additional information
-
construction of a PARN disruption mutant, the mutant shows no phenotype
additional information
-
Cells overexpressing gene PARN-1 have increased deadenylase activity, overexpression of gene PARN-1 leads to PARN-1 affecting the steady-state level and decay rates of at least four different procyclic mRNAs. Depletion of all three PARNs, PARN-1, PARN-2, and PARN-3, using RNA interference in procyclic and bloodstream-form parasites, neither growth rates nor gross morphology are affected in PARN-depleted procyclic forms, and growth rates are only slightly reduced to 90% of control rates in PARN-depleted BF parasites. Following depletion of PARN-1 protein using PARN-1-specific antibodies, RNA-A60 degradation is abolished
additional information
-
Cells overexpressing gene PARN-1 have increased deadenylase activity, overexpression of gene PARN-1 leads to PARN-1 affecting the steady-state level and decay rates of at least four different procyclic mRNAs. Depletion of all three PARNs, PARN-1, PARN-2, and PARN-3, using RNA interference in procyclic and bloodstream-form parasites, neither growth rates nor gross morphology are affected in PARN-depleted procyclic forms, and growth rates are only slightly reduced to 90% of control rates in PARN-depleted BF parasites. Following depletion of PARN-1 protein using PARN-1-specific antibodies, RNA-A60 degradation is abolished
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45 - 55
thermal stability and aggregation kinetic parameters, the aggregation is dominated by a first-order kinetics, increase in t0 and the decrease in k implies that Mg2+ can inhibit the rate of enzyme aggregation, overview. Cofactor Mg2+ is also important to PARN stability against inactivation induced by heat treatment, but promotes thermal aggregation at high temperatures. Mg2+ significantly decreases the rate but increases the aggregate size of the 54 kDa wild-type enzyme in a concentration-dependent manner. Effect of mutations on the Mg2+-dependent enzyme thermal aggregation, overview
49
55 - 85
thermal denaturation of PARN in presence or absence of K+, overview
49
-
inactivation of the four PARNs at 49°C, p74 is more stable than p54, p54 is equally stable than mutant p54DR3H, mutant p54DR3H is more stable than mutant p74DR3H
49
-
in the absence of Mg2+, the activity of PARN decreases continuously with increasing temperature
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
K+ induces additional regular secondary structures and enhances PARN stability against heat-induced inactivation, unfolding and aggregation
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70C, stable for several months
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Cell lysis is performed in a buffer containing 400 mM NaCl, 50 mM Tris/HCl, pH 8.0, 2 mM ethylenediaminetetraacetic acid and 2 mM dithiothreitol. The supernatant of the lysate is loaded onto a glutathione-Sepharose column and is eluted with lysis buffer containing 30 mM reduced glutathione. Glutathione S-transferase-PARN-RNA-recognition motif is incubated with protease and a final gel filtration is performed using a buffer containing 300 mM NaCl, 20 mM Tris/HCl, pH 8.0, and 2 mM DTT. PARN-RNA-recognition motif is concentrated to 8.8 mg/ml using a vivaspin concentrator, and 7-methylguanosine triphosphate is added in 6fold molar excess. SeMet-containing PARN-RNA-recognition motif purification is analogous, with the exception that the DTT concentration is elevated to 5 mM.
His-tag affinity chromatography HiTrap Q HP and 7-Me-GTP-Sepharose affinity chromatography
-
of the recombinant protein
overview on conditions
PARNn purified by glutathione-Sepharose 4B, MonoQ and Superdex 200 gel filtration columns. truncated PARN including the putative cap-binding domain purified by TALON affinity resin. full length PARN purified by Ni-NTA column
Pop2p purified on Ni2+ column and by gel filtration, to homogeneity
recombinant GST-tagged C-terminal 133 amino acids of the PARN-1 from Escherichia coli strain BL21
-
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by affinity chromatography
-
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by metal affinity chromatography
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and gel filtration
recombinant His-tagged full-length enzyme and His-tagged enzyme fragment from Escherichia coli strain BL21(DE3)
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli strain Rosetta by nickel affinity tandem chromatography and anion exchange chromatography
recombinant wild-type and mutant E240A, D489A, and H529A CNOT6L nuclease domains from Escherichia coli
-
The wild type and mutant forms of the cap-binding domain of PARN are overexpressed in Escherichia coli BL21(DE3) cells, harvested by centrifugation and suspended in 20 mM Tris-HCl buffer containing 1 M NaCl, 30 mM imidazole, 1 mM 1,4-DL-dithiothreitol, 0.1 mg/ml lysozyme, DNaseI and protease inhibitor cocktail, and lyse with a sonicator. Cell debris and inclusion bodies are removed by centrifugation. The supernatant is loaded on a Ni2+-NTA-agarose column and the proteins are eluted with 20 mM Tris-HCl, 1 M NaCl and 200 mM imidazole.
to homogeneity
Unlabeled and [15N], [13C]-labeled PARN cap-binding domains used for NMR experiments are synthesized by the cell-free protein expression system. After reaction, proteins are isolated by Ni2+-affinity chromatography before removing of the His6-tag. Subsequent cation-exchange chromatography yields the purified cap-binding domain.
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
2 genes, expression and sequence analysis, genotyping of plants, expression of His-tagged wild-type and mutant PARN as functional C-terminal maltose-binding protein-fusion protein in Escherichia coli, expression of wild-type GST-tagged enzyme in Spodoptera frugiperda Sf9 cells using the baculovirus transfection system
-
AHG2, mutant with Arabidopsis abscisic acid hypersensitivity, expression induced by treatment with Arabidopsis abscisic acid, high salinity and osmotic stress
DNA fragment corresponding to amino acids 443-560 in the human PARN sequence cloned into pCR 2.1TOPO vector and subsequently subcloned into the pET19b vector, recombinant PARN or PARN mutants expressed in Escherichia coli strain BL21(DE3)
-
expressed as N-terminal His6-tagged polypeptide in Escherichia coli BL21(DE3)
expression of enzyme subunits in the two-hybrid system using strain L40, expression of lexA-tagged wild-type and mutant Pab1p, Pan2p, and Pan3p in Escherichia coli, expression of full-length and N-terminal constructs of factor Pbp1p in Escherichia coli, overview
-
expression of GFP-tagged wild-type and mutant Pab1p in Xpo1-1 cells at 23°C and at 37°C leading to hyperadenylation of SSA4 mRNA, phenotype or recombinant cells, overview
-
expression of the GST-tagged C-terminal 133 amino acids of the PARN-1 open reading, cloned into the pGEX-6P-1 bacterial expression vector, in Escherichia coli strain BL21
-
expression of wild-type and mutants of the truncated catalytic domain of human CNOT6L, residues 158-555, in Escherichia coli
-
gene PARN, DNA and amino acid sequence determination and analysis, genotyping, quantitative real-time PCR enzyme expression analysis
gene PARN, expression of His-tagged enzyme in Escherichia coli strain Bl21(DE3)
-
gene PARN, recombinant expression of His-tagged enzyme in Escherichia coli strain BL21(DE3)
gene PARN, recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli strain Rosetta
gene PNLDC1, human PNLDC1-1 and PNLDC1-2 exons arrangement, recombinant expression of EGFP-tagged enzyme in HEK-293 cells, enzyme HsPNLDC1 is produced in two isoforms by alternative splicing of the full-length transcript that contains 19 exons, the peptide residues 1-25 (MDVGADEFEESLPLLQELVQEADFV) of isoform 1 are replaced by the peptide residues 1-14 (MFCTRGLLFFAFLA) in isoform 2 (according to the NCBI annotation), recombinant expression of His-tagged enzyme in Escherichia coli
gene PNLDC1, recombinant expression of EGFP-tagged enzyme in HEK-293 cells, mouse PNLDC1 has one predicted isoform, recombinant expression of His-tagged enzyme in Escherichia coli
His-tagged full-length enzyme, comprising residues 1-639, and His-tagged enzyme fragment, PARN(443-560), containing the RNA recognition motif with a 50 amino acids long C-terminal tail, comprising residues 443-560, are expressed in Escherichia coli strain BL21(DE3)
plasmid pET33 containing the human parn gene expressed in Escherichia coli BL21(DE3)
-
The DNA fragment encoding the cap-binding domain of PARN (residues 430-516) is amplified from a cDNA clone by PCR and is subcloned into pCR2.1. The cap-binding domain is expressed with a His6-tail, a protease cleavage site, a (Gly-Gly-Ser)2-Gly sequence at the N-terminus and a Ser-Gly-Pro-Ser-Ser-Gly sequence at the C-terminus. Deletion mutants of PARN that contain the cap-binding domain and its N- and/or C-terminal flanking regions, encoding residues 420-506, 420-516, 420-536, 430-506, 430-516 and 430-536, are amplified by PCR and subcloned into pET15b. Selected point mutations are introduced into the cap-binding domain (residues 430-516) using a site-directed mutagenesis kit. The wild type and mutant forms of the cap-binding domain of PARN are overexpressed in Escherichia coli.
The PARN fragment comprising amino acids 445-540 is amplified from a human cDNA library and cloned into the expression vector, the glutathione S-transferase-PARN-RNA-recognition motif fusion protein is expressed in Escherichia coli BL21(DE3). PARN mutants are generated from the wild-type clone (pGEX-6P-1 PARN445-540) using a Site-Directed Mutagenesis Kit. SeMet-containing PARN-RNA-recognition motif is expressed in Escherichia coli.
wild-type and mutant proteins transformed into Escherichia coli Rosetta (DE3) or Rosetta (DE3) pLysS cells
expressed as N-terminal His6-tagged polypeptide in Escherichia coli BL21(DE3)
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
nocturin deadenylase shows rhythmic expression under circadian control. It is rapidly induced in response to serum shock, LPS and other stimuli
nocturnin is rhythmically expressed in the cytoplasm of the retinal retina photoreceptor cells, with peak mRNA levels in the early night
the expression of several deadenylases is altered in squamous cell lung cancer, SCC. Quantitative real-time PCR shows that four deadenylases, PARN, CNOT6, CNOT7 and NOC, are differentially expressed in SCC clinical samples. PARN overexpression correlates with younger patient age and CNOT6 overexpression with non-metastatic tumors. Kaplan-Meier analysis suggests that increased levels of PARN and NOC correlate with significantly increased survival. The gene expression deregulation is functionally enriched for gene ontologies related to cell adhesion, cell junction, muscle contraction and metabolism
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
development of a high-throughput PARN inhibition assay in which fluorescence is used for monitoring PARN activity
diagnostics
clinical significance of deadenylases PARN and NOC on the survival in SCC diagnosed patients
medicine
additional information
medicine
-
leukemic cells from patients with acute lymphoblastic leukemia and acute myeloid leukemia display altered expression for CNOT6, CNOT6L, CNOT7 deadenylase and poly(A)-specific ribonuclease with most significant alterations for poly(A)-specific ribonuclease and CNOT7 mRNA levels. In acute lymphoblastic leukemia, a significant amount of poly(A)-specific ribonuclease is phosphorylated
medicine
expression of PARN in esophageal cancer tissues is higher than that in adjacent normal tissues, and the level of PARN expression is significantly positively correlated with lymphatic metastasis. Patients with high PARN levels have poor overall survival. The tumor volume and weight of nude mice treated with sh-PARN are significantly decreased
additional information
-
R3H domain may stabilize PARN by acting as a protector or intermolecular chaperone of the RRM domain
additional information
-
Mg2+ has dual effects on PARN stability, protecting the active site against denaturation, but destabilizing the overall structural stability of the protein
additional information
-
RRM motif of PARN harbors both poly(A) and cap binding properties, RRM plays an important role in PARN activity, i.e. recognition and dependence on both the cap structure and poly(A) tail during poly(A) hydrolysis. Trp475 plays an essential role in PARN cap recognition, whereas Glu455 and especially Trp456 play auxiliary roles. Cap binding is not essential for the hydrolytic activity of PARN. Cap and RNA-binding sites of the RRM are structurally and functionally separated from each other
additional information
-
the entire RRM domain not only contributes to the substrate binding and efficient catalysis of PARN, but also stabilizes the overall structures of the protein. p46 contains only one Trp residue (W219), p54 contains two (W219 and W456), and p74 contains six (W219, W456, W474, W526, W531 and W639)
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Homo sapiens (O95453), Homo sapiens
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Homo sapiens (O95453), Homo sapiens
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Homo sapiens (Q8NA58), Homo sapiens, Mus musculus (B2RXZ1), Mus musculus
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Homo sapiens (O95453), Homo sapiens
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Homo sapiens (O95453), Homo sapiens
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25
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Homo sapiens (O95453)
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Mus musculus (O35710), Mus musculus (Q8VDG3), Homo sapiens (O95453)
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Mus musculus (O35710)
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Cells
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836
2019
Homo sapiens (O95453)
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Duan, T.L.; Jiao, H.; He, G.J.; Yan, Y.B.
Translation efficiency and degradation of ER-associated mRNAs modulated by ER-anchored poly(A)-specific ribonuclease (PARN)
Cells
9
162
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Homo sapiens (O95453)
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Dodson, L.M.; Baldan, A.; Nissbeck, M.; Gunja, S.M.R.; Bonnen, P.E.; Aubert, G.; Birchansky, S.; Virtanen, A.; Bertuch, A.A.
From incomplete penetrance with normal telomere length to severe disease and telomere shortening in a family with monoallelic and biallelic PARN pathogenic variants
Hum. Mutat.
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2019
Homo sapiens (O95453)
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Dejene, E.A.; Li, Y.; Showkatian, Z.; Ling, H.; Seto, E.
Regulation of poly(A)-specific ribonuclease activity by reversible lysine acetylation
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295
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Homo sapiens (O95453)
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Kanazawa, M.; Ikeda, Y.; Nishihama, R.; Yamaoka, S.; Lee, N.H.; Yamato, K.T.; Kohchi, T.; Hirayama, T.
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Plant Cell Physiol.
61
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Marchantia polymorpha
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Armbruster, L.; Uslu, V.V.; Wirtz, M.; Hell, R.
The recovery from sulfur starvation is independent from the mRNA degradation initiation enzyme PARN in Arabidopsis
Plants (Basel)
8
380
2019
Arabidopsis thaliana (Q9LG26)
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Identification of PARN nuclease activity inhibitors by computational-based docking and high-throughput screening
Sci. Rep.
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5244
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Homo sapiens (O95453)
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Zhang, F.W.; Xie, X.W.; Chen, M.H.; Tong, J.; Chen, Q.Q.; Feng, J.; Chen, F.T.; Liu, W.Q.
Poly(A)-specific ribonuclease protein promotes the proliferation, invasion and migration of esophageal cancer cells
World J. Gastroenterol.
29
4783-4796
2023
Homo sapiens (O95453)
brenda
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Release 2026.1 (March 2026)
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