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(A)6 + H2O
5'-AMP + ?
-
-
-
?
poly(A) + H2O
5'-AMP + ?
average substrate length about 200 A
-
-
?
poly(A) RNA + H2O
5'-AMP + ?
poly(A)-mRNA + H2O
5'-AMP
polyadenylated RNA containing AU-rich elements + H2O
RNA containing AU-rich elements + AMP
-
-
?
additional information
?
-
18S-E pre-rRNA + H2O
?
-
-
-
?
18S-E pre-rRNA + H2O
?
different 18S-E pre-rRNAs
-
-
?
miR-362-5p + H2O
?
miR-362-5p is defined by DROSHA and DICER to 26 nt in length
-
-
?
miR-362-5p + H2O
?
a mammalian miRNA whose precursor contains a relatively large bulge compared with other premiRNAs. Primer extension analysis of miR-362-5p
-
-
?
poly(A) + H2O
AMP
-
-
-
-
ir
poly(A) + H2O
AMP
-
-
-
ir
poly(A) RNA + H2O
5'-AMP + ?
-
-
-
-
?
poly(A) RNA + H2O
5'-AMP + ?
-
-
-
?
poly(A) RNA + H2O
5'-AMP + ?
-
one RNA-binding domain is required for the substrate binding, but not for the catalysis of PARN
-
-
?
poly(A) RNA + H2O
5'-AMP + ?
-
the RRM of PARN binds RNA
-
-
?
poly(A) RNA + H2O
5'-AMP + ?
-
deadenylation of mRNA
-
-
?
poly(A)-mRNA + H2O
5'-AMP
-
-
-
?
poly(A)-mRNA + H2O
5'-AMP
-
-
?
poly(A)-mRNA + H2O
5'-AMP
DAN involved in oocyte maturation
-
-
?
additional information
?
-
Poly(A)-specific ribonuclease is a eukaryotic enzyme that efficiently degrades mRNA poly(A) tails
-
-
?
additional information
?
-
-
Poly(A)-specific ribonuclease is a eukaryotic enzyme that efficiently degrades mRNA poly(A) tails
-
-
?
additional information
?
-
-
enzyme is 5-6 times more active if the substrate is m7G(5)ppp(5)G capped
-
?
additional information
?
-
-
physiological role of enzyme, recognition mechanisms that target mRNA for degradation
-
?
additional information
?
-
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
-
-
?
additional information
?
-
-
PARN specifically degrades the mRNA poly(A) tails with a free 3'-hydroxyl group and releases 5'-AMP as the mononucleotide product
-
-
?
additional information
?
-
-
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
-
-
?
additional information
?
-
active site structure, modelling, overview
-
-
?
additional information
?
-
-
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
-
-
?
additional information
?
-
-
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
-
-
?
additional information
?
-
-
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+
-
-
?
additional information
?
-
Poly(A)-specific ribonuclease (PARN) is a deadenylase that processes mRNAs and non-coding RNA
-
-
?
additional information
?
-
-
Poly(A)-specific ribonuclease (PARN) is a deadenylase that processes mRNAs and non-coding RNA
-
-
?
additional information
?
-
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)
-
-
?
additional information
?
-
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)
-
-
?
additional information
?
-
-
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)
-
-
?
additional information
?
-
enzyme PARN performs exonucleolytic trimming of 18S-E pre-rRNA, and PARN can process the corresponding ITS1 RNA fragment in vitro
-
-
?
additional information
?
-
-
enzyme PARN performs exonucleolytic trimming of 18S-E pre-rRNA, and PARN can process the corresponding ITS1 RNA fragment in vitro
-
-
?
additional information
?
-
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
-
-
?
additional information
?
-
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)
-
-
?
additional information
?
-
-
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)
-
-
?
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1-(3',4'-dideoxy-3'-fluoro-beta-D-glucopyranosyl) cytosine
-
1-(3',4'-dideoxy-3'-fluoro-beta-D-glucopyranosyl)-N4-benzoyl cytosine
-
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)-3,7-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-(phenoxymethyl)-3,7-dihydro-1H-purine-2,6-dione
-
1-hydroxy-7-(pyridin-2-yl)-3,7-dihydro-1H-purine-2,6-dione
-
1-hydroxy-7-(pyridin-3-yl)-3,7-dihydro-1H-purine-2,6-dione
-
1-hydroxy-7-(pyridin-4-yl)-3,7-dihydro-1H-purine-2,6-dione
-
1-hydroxy-7-phenyl-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-(2-butoxyethyl)-1-hydroxy-3,7-dihydro-1H-purine-2,6-dione
-
7-benzyl-1-hydroxy-3,7-dihydro-1H-purine-2,6-dione
-
7-benzyl-1-[(prop-2-en-1-yl)oxy]-3,7-dihydro-1H-purine-2,6-dione
-
7-benzyl-3,7-dihydro-1H-purine-2,6-dione
-
9-(3',4'-dideoxy-3'-fluoro-beta-D-glucopyranosyl)-N6-benzoyl adenine
-
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
Ca2+
-
3 mM gradually decreases activity about 15fold
cap analogue 7-methylguanosine(5')ppp(5')G
-
allosteric inhibitor of PARN in the presence of a physiological K+ concentration
Co2+
-
3 mM gradually decreases activity about 78fold
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
eIF4E
-
competition between PARN and eIF4E for the 5'-cap
-
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
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
Mn2+
-
3 mM gradually decreases activity about 5fold
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)-binding protein PAB 1
-
poly[2'-O-(2,4-dinitrophenyl)]poly-(A)
competitive
-
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
-
AMP
-
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
Poly(A)
-
Poly(A)
strong inhibition of both spermidine- and polyadenylate-binding protein-activated hPAN complex
poly(A)-binding protein PAB 1
phased poly(A) shortening
-
poly(A)-binding protein PAB 1
inhibits
-
poly(C)
-
poly(C)
strong inhibition of spermidine-, slight inhibition of polyadenylate-binding protein-activated hPAN complex
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
-
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
-
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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.
Anemia
Insufficient liver maturation affects murine early postnatal hair cycle.
Arthritis
The Acute-phase Response Is Not Predictive for the Development of Arthritis in Seropositive Arthralgia - A Prospective Cohort Study.
Azoospermia
Variant PNLDC1, Defective piRNA Processing, and Azoospermia.
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.
Carcinogenesis
The mammalian anti-proliferative BTG/Tob protein family.
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.
Hepatitis
Insufficient liver maturation affects murine early postnatal hair cycle.
HIV Infections
A Quantitative Genetic Interaction Map of HIV Infection.
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.
Infections
Poliovirus Mediated Disruption of Cytoplasmic Processing Bodies.
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
Milk-specific RNase as a marker of differentiation of rat mammary tumors.
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 (PARN): More than just "mRNA stock clearing".
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 mammalian anti-proliferative BTG/Tob protein family.
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
mRNA deadenylation and telomere disease.
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
Homozygous Rare PARN Missense Mutation in Familial Pulmonary Fibrosis.
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
The molecular genetics of the telomere biology disorders.
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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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
0.0106 - 0.119
1-hydroxy-7-(pyridin-2-yl)-3,7-dihydro-1H-purine-2,6-dione
0.0066 - 0.125
1-hydroxy-7-(pyridin-3-yl)-3,7-dihydro-1H-purine-2,6-dione
0.0233 - 0.245
1-hydroxy-7-(pyridin-4-yl)-3,7-dihydro-1H-purine-2,6-dione
0.0104 - 0.0841
1-hydroxy-7-phenyl-3,7-dihydro-1H-purine-2,6-dione
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
0.0239
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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evolution
PARN is a member of the DEDD family of 3'-to-5' exonucleases with a marked nucleotide preference towards A
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
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
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
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
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
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 enzyme plays a role in mRNA catabolism and in exonucleolytic trimming of 18S-E pre-rRNA
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
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
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
deadenylation regulates RNA function and fate. Poly(A)-specific ribonuclease (PARN) is a deadenylase that processes mRNAs and non-coding RNA
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
PNLDC1 is a deadenylase that is excluded from the nucleus and most likely, its function occurs mainly in the endoplasmic reticulum
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
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
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
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
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
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
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
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
-
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
mechanisms of PARN-mediated miRNA shortening
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
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
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D478A
generated by site-directed mutagenesis, Kd value for 7-methylguanosine triphosphate is 20.0 microM
D489A
-
site-directed mutagenesis, active site mutant, inactive mutant
E240A
-
site-directed mutagenesis, active site mutant, inactive mutant
E455/W456/W475A
-
severely defective in cap binding, active deadenylase
E455A
-
no defect in its cap binding
F484A
-
site-directed mutagenesis, active site mutant, not expressable in Escherichia coli
H377A
site-directed mutagenesis, catalytic inactive mutant
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
H529A
-
site-directed mutagenesis, active site mutant, inactive mutant
K454A
generated by site-directed mutagenesis, Kd value for 7-methylguanosine triphosphate is 20.03 microM
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
-
site-directed mutagenesis, activity and kinetics with RNA substrates compared to the wild-type enzyme
N412A
-
site-directed mutagenesis, active site mutant, not expressable in Escherichia coli
P365A
-
site-directed mutagenesis, active site mutant, not expressable in Escherichia coli
P365A/F484A
-
site-directed mutagenesis, active site mutant, not expressable in Escherichia coli
P365A/N412A/F484A
-
site-directed mutagenesis, active site mutant, not expressable in Escherichia coli
T458A
generated by site-directed mutagenesis, Kd value for 7-methylguanosine triphosphate is 30.58 microM
W456A
-
cap binding slightly affected
W475A
-
severely defective in cap binding
D28A
-
catalytically inactive, RNA-binding is not affected
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
-
catalytically inactive, RNA-binding is not affected
D292A
site-directed mutagenesis, structure comparison to the wild-type enzyme, the mutant shows unaltered ellipticity
D382A
-
catalytically inactive, RNA-binding is not affected
D382A
site-directed mutagenesis, structure comparison to the wild-type enzyme, the mutant shows slightly decreased ellipticity
E30A
-
catalytically inactive, RNA-binding is not affected
E30A
site-directed mutagenesis, structure comparison to the wild-type enzyme, the mutant shows significantly decreased ellipticity
additional information
-
PARN(443-560/W456/W475A) mutant is severely defective in cap binding, has RNA binding properties
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
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
enzyme knockout by siRNA in HeLa cells
additional information
-
enzyme knockout by siRNA in HeLa 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
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
-
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
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Korner, C.G.; Wormington, M.; Muckenthaler, M.; Schneider, S.; Dehlin, E.; Wahle, E.
The deadenylating nuclease (DAN) is involved in poly(A) tail removal during the meiotic maturation of Xenopus oocytes
EMBO J.
17
5427-5437
1998
Bos taurus, Xenopus sp., Homo sapiens (O95453), Homo sapiens
brenda
Ren, Y.G.; Martinez, J.; Virtanen, A.
Identification of the active site of poly(A)-specific ribonuclease by site-directed mutagenesis and Fe(2+)-mediated cleavage
J. Biol. Chem.
277
5982-5987
2002
Homo sapiens
brenda
Uchida, N.; Hoshino, S.i.; Katada, T.
Identification of a human cytoplasmic poly(A) nuclease complex stimulated by poly(A)-binding protein
J. Biol. Chem.
279
1383-1391
2004
Homo sapiens (Q504Q3), Homo sapiens
brenda
Virtanen, A.; Martinez, J.; Ren, Y.G.
Purification of poly(A)-specific ribonuclease
Methods Enzymol.
342
303-309
2001
Bos taurus, Homo sapiens, Xenopus sp.
brenda
Gao, M.; Fritz, D.T.; Ford, L.P.; Wilusz, J.
Interaction between a poly(A)-specific ribonuclease and the 5' cap influences mRNA deadenylation rates in vitro
Mol. Cell
5
479-488
2000
Homo sapiens
brenda
Lai, W.S.; Kennington, E.A.; Blackshear, P.J.
Tristetraprolin and its family members can promote the cell-free deadenylation of AU-rich element-containing mRNAs by poly(A) ribonuclease
Mol. Cell. Biol.
23
3798-3812
2003
Homo sapiens (O95453)
brenda
Wu, M.; Reuter, M.; Lilie, H.; Liu, Y.; Wahle, E.; Song, H.
Structural insight into poly(A) binding and catalytic mechanism of human PARN
EMBO J.
24
4082-4093
2005
Homo sapiens (O95453), Homo sapiens
brenda
Nilsson, P.; Virtanen, A.
Expression and purification of recombinant poly(A)-specific ribonuclease (PARN)
Int. J. Biol. Macromol.
39
1-3
2006
Homo sapiens
brenda
Seal, R.; Temperley, R.; Wilusz, J.; Lightowlers, R.N.; Chrzanowska-Lightowlers, Z.M.
Serum-deprivation stimulates cap-binding by PARN at the expense of eIF4E, consistent with the observed decrease in mRNA stability
Nucleic Acids Res.
33
376-387
2005
Homo sapiens
brenda
Zhang, A.; Liu, W.F.; Yan, Y.B.
Role of the RRM domain in the activity, structure and stability of poly(A)-specific ribonuclease
Arch. Biochem. Biophys.
461
255-262
2007
Homo sapiens
brenda
Liu, W.; Zhang, A.; He, G.; Yan, Y.
The R3H domain stabilizes poly(A)-specific ribonuclease by stabilizing the RRM domain
Biochem. Biophys. Res. Commun.
360
846-851
2007
Homo sapiens
brenda
Liu, W.F.; Zhang, A.; Cheng, Y.; Zhou, H.M.; Yan, Y.B.
Effect of magnesium ions on the thermal stability of human poly(A)-specific ribonuclease
FEBS Lett.
581
1047-1052
2007
Homo sapiens
brenda
Nilsson, P.; Henriksson, N.; Niedzwiecka, A.; Balatsos, N.A.; Kokkoris, K.; Eriksson, J.; Virtanen, A.
A multifunctional RNA recognition motif in poly(A)-specific ribonuclease with cap and poly(A) binding properties
J. Biol. Chem.
282
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2007
Homo sapiens
brenda
Liu, W.F.; Zhang, A.; Cheng, Y.; Zhou, H.M.; Yan, Y.B.
Allosteric regulation of human poly(A)-specific ribonuclease by cap and potassium ions
Biochem. Biophys. Res. Commun.
379
341-345
2009
Homo sapiens
brenda
Monecke, T.; Schell, S.; Dickmanns, A.; Ficner, R.
Crystal structure of the RRM domain of poly(A)-specific ribonuclease reveals a novel m(7)G-cap-binding mode
J. Mol. Biol.
382
827-834
2008
Homo sapiens (O95453)
brenda
Balatsos, N.A.; Vlachakis, D.; Maragozidis, P.; Manta, S.; Anastasakis, D.; Kyritsis, A.; Vlassi, M.; Komiotis, D.; Stathopoulos, C.
Competitive inhibition of human poly(A)-specific ribonuclease (PARN) by synthetic fluoro-pyranosyl nucleosides
Biochemistry
48
6044-6051
2009
Homo sapiens (O95453), Homo sapiens
brenda
Balatsos, N.A.; Anastasakis, D.; Stathopoulos, C.
Inhibition of human poly(A)-specific ribonuclease (PARN) by purine nucleotides: kinetic analysis
J. Enzyme Inhib. Med. Chem.
24
516-523
2009
Homo sapiens
brenda
Niedzwiecka, A.; Lekka, M.; Nilsson, P.; Virtanen, A.
Global architecture of human poly(A)-specific ribonuclease by atomic force microscopy in liquid and dynamic light scattering
Biophys. Chem.
158
141-149
2011
Homo sapiens (Q96LI5), Homo sapiens
brenda
Wang, H.; Morita, M.; Yang, X.; Suzuki, T.; Yang, W.; Wang, J.; Ito, K.; Wang, Q.; Zhao, C.; Bartlam, M.; Yamamoto, T.; Rao, Z.
Crystal structure of the human CNOT6L nuclease domain reveals strict poly(A) substrate specificity
EMBO J.
29
2566-2576
2010
Homo sapiens
brenda
He, G.J.; Liu, W.F.; Yan, Y.B.
Dissimilar roles of the four conserved acidic residues in the thermal stability of poly(a)-specific ribonuclease
Int. J. Mol. Sci.
12
2901-2916
2011
Homo sapiens (O95453)
brenda
Henriksson, N.; Nilsson, P.; Wu, M.; Song, H.; Virtanen, A.
Recognition of adenosine residues by the active site of poly(A)-specific ribonuclease
J. Biol. Chem.
285
163-170
2010
Homo sapiens
brenda
Maragozidis, P.; Karangeli, M.; Labrou, M.; Dimoulou, G.; Papaspyrou, K.; Salataj, E.; Pournaras, S.; Matsouka, P.; Gourgoulianis, K.I.; Balatsos, N.A.
Alterations of deadenylase expression in acute leukemias: evidence for poly(A)-specific ribonuclease as a potential biomarker
Acta Haematol.
128
39-46
2012
Homo sapiens
brenda
He, G.J.; Zhang, A.; Liu, W.F.; Yan, Y.B.
Distinct roles of the R3H and RRM domains in poly(A)-specific ribonuclease structural integrity and catalysis
Biochim. Biophys. Acta
1834
1089-1098
2013
Homo sapiens (O95453)
brenda
He, G.J.; Yan, Y.B.
Self-association of poly(A)-specific ribonuclease (PARN) triggered by the R3H domain
Biochim. Biophys. Acta
1844
2077-2085
2014
Homo sapiens (O95453)
brenda
Yoda, M.; Cifuentes, D.; Izumi, N.; Sakaguchi, Y.; Suzuki, T.; Giraldez, A.J.; Tomari, Y.
Poly(A)-specific ribonuclease mediates 3-end trimming of Argonaute2-cleaved precursor microRNAs
Cell Rep.
5
715-726
2013
Homo sapiens
brenda
Vlachakis, D.; Pavlopoulou, A.; Tsiliki, G.; Komiotis, D.; Stathopoulos, C.; Balatsos, N.; Kossida, S.
An integrated in silico approach to design specific inhibitors targeting human poly(A)-specific ribonuclease
PLoS ONE
7
e51113
2012
Homo sapiens (O95453), Homo sapiens
brenda
He, G.; Yan, Y.
Contributions of the C-terminal domain to poly(A)-specific ribonuclease (PARN) stability and self-association
Biochem. Biophys. Rep.
18
100626
2019
Homo sapiens (O95453)
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brenda
Zhang, L.; Yan, Y.
Depletion of poly(A)-specific ribonuclease (PARN) inhibits proliferation of human gastric cancer cells by blocking cell cycle progression
Biochim. Biophys. Acta
1853
522-534
2015
Homo sapiens (O95453), Homo sapiens
brenda
Niedzwiecka, A.; Nilsson, P.; Worch, R.; Stepinski, J.; Darzynkiewicz, E.; Virtanen, A.
Molecular recognition of mRNA 5' cap by 3' poly(A)-specific ribonuclease (PARN) differs from interactions known for other cap-binding proteins
Biochim. Biophys. Acta
1864
331-345
2016
Homo sapiens (O95453)
brenda
Jadhav, G.; Kaur, I.; Maryati, M.; Airhihen, B.; Fischer, P.; Winkler, G.
Discovery, synthesis and biochemical profiling of purine-2,6-dione derivatives as inhibitors of the human poly(A)-selective ribonuclease Caf1
Bioorg. Med. Chem. Lett.
25
4219-4224
2015
Homo sapiens (O95453), Homo sapiens (Q9UIV1), Homo sapiens
brenda
Dhanraj, S.; Gunja, S.M.; Deveau, A.P.; Nissbeck, M.; Boonyawat, B.; Coombs, A.J.; Renieri, A.; Mucciolo, M.; Marozza, A.; Buoni, S.; Turner, L.; Li, H.; Jarrar, A.; Sabanayagam, M.; Kirby, M.; Shago, M.; Pinto, D.; Berman, J.N.; Scherer, S.W.; Virtanen, A.; Dror, Y.
Bone marrow failure and developmental delay caused by mutations in poly(A)-specific ribonuclease (PARN)
J. Med. Genet.
52
738-748
2015
Homo sapiens (O95453), Homo sapiens
brenda
Maragozidis, P.; Papanastasi, E.; Scutelnic, D.; Totomi, A.; Kokkori, I.; Zarogiannis, S.G.; Kerenidi, T.; Gourgoulianis, K.I.; Balatsos, N.A.
Poly(A)-specific ribonuclease and Nocturnin in squamous cell lung cancer prognostic value and impact on gene expression
Mol. Cancer
14
187
2015
Homo sapiens (O95453), Homo sapiens
brenda
Moon, D.H.; Segal, M.; Boyraz, B.; Guinan, E.; Hofmann, I.; Cahan, P.; Tai, A.K.; Agarwal, S.
Poly(A)-specific ribonuclease (PARN) mediates 3'-end maturation of the telomerase RNA component
Nat. Genet.
47
1482-1488
2015
Homo sapiens (O95453), Homo sapiens
brenda
Anastasakis, D.; Skeparnias, I.; Shaukat, A.N.; Grafanaki, K.; Kanellou, A.; Taraviras, S.; Papachristou, D.J.; Papakyriakou, A.; Stathopoulos, C.
Mammalian PNLDC1 is a novel poly(A) specific exonuclease with discrete expression during early development
Nucleic Acids Res.
44
8908-8920
2016
Homo sapiens (Q8NA58), Homo sapiens, Mus musculus (B2RXZ1), Mus musculus
brenda
Ishikawa, H.; Yoshikawa, H.; Izumikawa, K.; Miura, Y.; Taoka, M.; Nobe, Y.; Yamauchi, Y.; Nakayama, H.; Simpson, R.J.; Isobe, T.; Takahashi, N.
Poly(A)-specific ribonuclease regulates the processing of small-subunit rRNAs in human cells
Nucleic Acids Res.
45
3437-3447
2017
Homo sapiens (O95453), Homo sapiens
brenda
Montellese, C.; Montel-Lehry, N.; Henras, A.K.; Kutay, U.; Gleizes, P.E.; ODonohue, M.F.
Poly(A)-specific ribonuclease is a nuclear ribosome biogenesis factor involved in human 18S rRNA maturation
Nucleic Acids Res.
45
6822-6836
2017
Homo sapiens (O95453), Homo sapiens
brenda
Lee, D.; Park, D.; Park, J.; Kim, J.; Shin, C.
Poly(A)-specific ribonuclease sculpts the 3' ends of microRNAs
RNA
25
388-405
2019
Homo sapiens (O95453)
-
brenda
Godwin, A.; Kojima, S.; Green, C.; Wilusz, J.
Kiss your tail goodbye The role of PARN, Nocturnin, and Angel deadenylases in mRNA biology
Biochim. Biophys. Acta
1829
571-579
2013
Mus musculus (O35710), Mus musculus (Q8VDG3), Homo sapiens (O95453)
brenda