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Information on EC 2.7.7.8 - polyribonucleotide nucleotidyltransferase and Organism(s) Homo sapiens and UniProt Accession Q8TCS8
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2.7.7.8 polyribonucleotide nucleotidyltransferaseIUBMB Comments
ADP, IDP, GDP, UDP and CDP can act as donors.
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Word Map
- 2.7.7.8
- rnase
- exoribonuclease
- polya
- ribonuclease
- polymerization
-
polyadenylation
-
phosphorolysis
-
degradosome
- helicase
-
exonuclease
-
exonucleolytic
-
stem-loop
- luteus
- micrococcus
- 5'-diphosphate
-
rna-binding
- kh
- hfq
- oligoribonucleotides
-
rna-degrading
-
heteropolymeric
- antibioticus
-
dead-box
- lysodeikticus
-
primer-independent
- synthesis
- molecular biology
- medicine
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
polynucleotide phosphorylase, hpnpase(old-35), pnpt1, polyribonucleotide nucleotidyltransferase, atmtpnpase, cppnpase, hpnpaseold-35, chloroplast pnpase, polyribonucleotide phosphorylase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
nucleoside diphosphate:polynucleotidyl transferase
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nucleotidyltransferase, polyribonucleotide
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-
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PNPase
polynucleotide phosphorylase
polyribonucleotide phosphorylase
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PNPase
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polynucleotide phosphorylase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
RNAn+1 + phosphate = RNAn + a nucleoside diphosphate
mechanism of elongation, overview
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
nucleotidyl group transfer
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SYSTEMATIC NAME
IUBMB Comments
polyribonucleotide:phosphate nucleotidyltransferase
ADP, IDP, GDP, UDP and CDP can act as donors.
CAS REGISTRY NUMBER
COMMENTARY
9014-12-4
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
24-nucleotide RNA molecule + ADP
25-nucleotide RNA molecule + phosphate
-
when both ADP and phosphate are present at the reaction mixture, the direction of activity, either polyadenylation or degradation, is dependent on their relative concentrations
-
-
r
24-nucleotide RNA molecule + phosphate
23-nucleotide RNA molecule + nucleoside diphosphate
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when both ADP and phosphate are present at the reaction mixture, the direction of activity, either polyadenylation or degradation, is dependent on their relative concentrations
-
-
r
microR-221 RNAn+1 + phosphate
microR-221 RNAn + ADP
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recombinantly expressed microRNAs miR-let7a, miR-106b, miR-25, miR-221, miR-222, and miR-184 as substrates, the recombinant enzyme selectively and preferentially degrades microRNA-221 in human melanoma cells
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-
r
microRNAn+1 + phosphate
microRNAn + ADP
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recombinantly expressed microRNAs miR-let7a, miR-106b, miR-25, miR-221, miR-222, and miR-184
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-
r
RNAn + a nucleoside diphosphate
RNAn+1 + phosphate
-
specificity overview
-
r
RNAn+1 + phosphate
RNAn + a nucleoside diphosphate
-
enhanced expression of hPNPase(old-35) via a replication-incompetent adenovirus (Ad.hPNPase(old-35)) in human melanoma cells and normal melanocytes results in a characteristic sensecence-like phenotype. Overexpression of hPNPase(old-35) results in increased production of ROS, leading to activation of the nuclear factor (NF)-kappaB pathway. Ad.hPNPase(old-35) infection promotes degradation of IkappaBalpha and nuclear translocation of NF-kappaB and markedly increased binding of the transcriptional activator p50/p65. Infection with (Ad.hPNPase(old-35)) enhances the production of interleukin-6 and interleukin-8, two classical NF-kappaB-responsive cytokines. hPNPase(old-35) might play a significant role in producing pathological changes associated with aging be generating proinflammatory cytokines via ROS and NF-kappaB
-
-
?
RNAn+1 + phosphate
RNAn + a nucleoside diphosphate
-
poly(A) length of human mitochondrial mRNAs is controlled by polyadenylation by poly(A) polymerase and deadenylation by polynucleotide phosphorylase. Polyadenylation is required for stability of mitochondrial mRNAs
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-
?
RNAn+1 + phosphate
RNAn + a nucleoside diphosphate
the enzyme catalyzes the processive phosphorolysis of RNA by using an inorganic phosphate to cleave the phosphodiester linkage at the 3'-end of a RNA chain
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-
?
RNAn+1 + phosphate
RNAn + a nucleoside diphosphate
the functional trimeric phosphorylase is capable of digesting single-stranded RNA to produce final products of about 4 nt in length
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-
?
additional information
?
-
-
enzyme may play a role in excluding oxidized forms of RNA from the translation mechanism
-
-
?
additional information
?
-
-
polynucleotide phosphorylase is involved in protecting cells and limiting damaged RNA under oxidative conditions
-
-
?
additional information
?
-
-
the apoptosis-inducing activity of polynucleotide phosphorylase is mediated by activation of double-stranded RNAdependent protein kinase. Activation of RNA-dependent protein kinase by polynucleotide phosphorylase precedes phosphorylation of eukaryotic initiation factor-2A and induction of growth arrest and DNA damage-inducible gene 153, GADD153, that culminates in the shutdown of protein synthesis and apoptosis. Activation of RNA-dependent protein kinase by polynucleotide phosphorylase also instigates down-regulation of the antiapoptotic protein Bcl-xL
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-
?
additional information
?
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no activity with ATP nor the other NTPs, as well as mono phosphate nucleotides. Enzyme degrades polyadenylated and nonpolyadenylated RNA at similar rates
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-
?
additional information
?
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-
suppressor of Var1 3 and polynucleotide phosphorylase form a 330-kDa heteropentamer that is capable of efficiently degrading double-stranded RNA substrates in the presence of ATP, the hSUV3-PNPase complex prefers substrates containing a 3' overhang and degrades the RNA in a 3'-to-5' directionality
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-
?
additional information
?
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-
PNPase, as a phosphorylase, incorporates phosphate and ADP in degradation and polymerization process, respectively. The specificity of the enzyme for the polymerization reaction is high for ADP, with much less activity for other nucleotide diphosphates and no activity for ATP or other nucleotide triphosphates. The human PNPase displays no preferential activity for polyadenylated RNA like bacterial or chloroplast PNPase
-
-
?
additional information
?
-
full-length and DELTAS1 hPNPase cleave the poly(A)12 and poly(U)12 RNA with similar activities and DELTAS1 hPNPase cleaves ssRNA substrate almost as efficiently as full-length PNPase
-
-
?
additional information
?
-
-
full-length and DELTAS1 hPNPase cleave the poly(A)12 and poly(U)12 RNA with similar activities and DELTAS1 hPNPase cleaves ssRNA substrate almost as efficiently as full-length PNPase
-
-
?
additional information
?
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human polynucleotide phosphorylase hPNPaseold-35 is a type I IFN-inducible 3'-5' exoribonuclease, which degrades specific mRNAs and small noncoding RNAs. miR-221, a regulator of the cyclin-dependent kinase inhibitor p27kip1, displays robust downregulation with ensuing up-regulation of p27kip1 by expression of hPNPaseold-35,which also occurs in multiple human melanoma cells upon IFN-beta treatment
-
-
?
additional information
?
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-
in the cytoplasm, human enzyme, from adenoviral-mediated overexpression, can directly degrade c-myc mRNA by virtue of its 3'-5' exoribonuclease property, and this degradation is specific for c-myc as compared with other mRNAs, such as c-jun, glyceraldehyde 3-phosphate dehydrogenase or GADD 34. In melanoma cells, degradation of microR-221 by hPNPase is more profound compared with other miRNAs
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-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
RNAn+1 + phosphate
RNAn + a nucleoside diphosphate
-
enhanced expression of hPNPase(old-35) via a replication-incompetent adenovirus (Ad.hPNPase(old-35)) in human melanoma cells and normal melanocytes results in a characteristic sensecence-like phenotype. Overexpression of hPNPase(old-35) results in increased production of ROS, leading to activation of the nuclear factor (NF)-kappaB pathway. Ad.hPNPase(old-35) infection promotes degradation of IkappaBalpha and nuclear translocation of NF-kappaB and markedly increased binding of the transcriptional activator p50/p65. Infection with (Ad.hPNPase(old-35)) enhances the production of interleukin-6 and interleukin-8, two classical NF-kappaB-responsive cytokines. hPNPase(old-35) might play a significant role in producing pathological changes associated with aging be generating proinflammatory cytokines via ROS and NF-kappaB
-
-
?
RNAn+1 + phosphate
RNAn + a nucleoside diphosphate
-
poly(A) length of human mitochondrial mRNAs is controlled by polyadenylation by poly(A) polymerase and deadenylation by polynucleotide phosphorylase. Polyadenylation is required for stability of mitochondrial mRNAs
-
-
?
RNAn+1 + phosphate
RNAn + a nucleoside diphosphate
the enzyme catalyzes the processive phosphorolysis of RNA by using an inorganic phosphate to cleave the phosphodiester linkage at the 3'-end of a RNA chain
-
-
?
additional information
?
-
-
enzyme may play a role in excluding oxidized forms of RNA from the translation mechanism
-
-
?
additional information
?
-
-
polynucleotide phosphorylase is involved in protecting cells and limiting damaged RNA under oxidative conditions
-
-
?
additional information
?
-
-
the apoptosis-inducing activity of polynucleotide phosphorylase is mediated by activation of double-stranded RNAdependent protein kinase. Activation of RNA-dependent protein kinase by polynucleotide phosphorylase precedes phosphorylation of eukaryotic initiation factor-2A and induction of growth arrest and DNA damage-inducible gene 153, GADD153, that culminates in the shutdown of protein synthesis and apoptosis. Activation of RNA-dependent protein kinase by polynucleotide phosphorylase also instigates down-regulation of the antiapoptotic protein Bcl-xL
-
-
?
additional information
?
-
-
PNPase, as a phosphorylase, incorporates phosphate and ADP in degradation and polymerization process, respectively. The specificity of the enzyme for the polymerization reaction is high for ADP, with much less activity for other nucleotide diphosphates and no activity for ATP or other nucleotide triphosphates. The human PNPase displays no preferential activity for polyadenylated RNA like bacterial or chloroplast PNPase
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-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
hydrogen peroxide
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upon exposure of human cells, the amount of enzyme protein decreases rapidly
menadione
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upon exposure of human cells, the amount of enzyme protein decreases rapidly
additional information
-
no specific decrease in enzyme protein level upon treatment of cells with cycloheximide or ACNU, i.e. 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosurea hydrochloride
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
interferon-beta
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close association between interferon-beta induced upregulation of enzyme and c-myc downregulation
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
enzyme binding with RNA displays an apparent sigmoid curve, with a Kd of 16 nM
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
structure of the S1 pore in exosomes and the KH pore in hPNPase, overview
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localizes to the intermembrane space of mitochondria as a peripheral membrane protein in a multimeric complex
additional information
-
basal and interferon-beta induced enzyme is efficiently imported into mitochondria with coupled processing of the N-terminal targeting sequence. It localizes to the intermembrane space as a peripheral membrane protein in a multimeric complex
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mammalian PNPase contains an N-terminal mitochondrial localization signal facilitating its subcellular localization in mitochondria
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
evolution
-
human polynucleotide phosphorylase is an evolutionary conserved RNA-processing enzyme. PNPase contains five motifs that are conspicuously preserved through evolution extending from prokaryotes and plants to mammals. Although hPNPase structurally and biochemically resembles PNPase of other species, overexpression and inhibition studies reveal that hPNPase has evolved to serve more specialized and diversified functions in humans
malfunction
-
inhibition of the enzyme by shRNA or stable overexpression of miR-221 protects melanoma cells from IFN-beta-mediated growth inhibition
metabolism
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the enzyme is involved in RNA degradation and/turnover, major processes controlling RNA levels and important regulators of physiological and pathological processes
physiological function
additional information
physiological function
in cardiac tissue from human and mouse models of type 2 diabetes mellitus, levels of Argonaute2 protein, associated with cytosolic and mitochondrial miRNAs, are unchanged while PNPase protein expression levels are increased. There an increase in the association between both proteins in the diabetic state
physiological function
polynucleotide phosphorylase is involved in controlling the levels of RNA oxidation marker 8-hydrooxyguanosine in both cytoplasmic and mitochondrial fractions. Expression of exogenous polynucleotide phosphorylase reduces 8-hydrooxyguanosine levels in both cytoplasm and mitochondria. The S1 RNA binding domain is crucial for reducing 8-hydrooxyguanosine in both cytoplasm and mitochondria, while the N-terminal mitochondrial translocation signal is required for 8-hydrooxyguanosine reduction in mitochondria. One of the RPH1 or RPH2 domains is sufficient to reduce 8-hydrooxyguanosine levels in RNA under oxidative stress conditions
physiological function
-
hPNPaseold-35 regulates the expression of specific miRNAs, importance of hPNPaseold-35 induction and miR-221 downregulation in mediating IFN-beta action, mechanism of miRNA regulation involving selective enzymatic degradation, overview
physiological function
human polynucleotide phosphorylase is a 3'-to-5' exoribonuclease that degrades specific mRNA and miRNA, and imports RNA into mitochondria, and thus regulates diverse physiological processes, including cellular senescence and homeostasis
physiological function
-
polynucleotide phosphorylase is an RNA-processing enzyme with expanding roles in regulating cellular physiology. By executing exonuclease activity PNPase specifically degrades mature miRNAs, schematic model of microRNA biogenesis and stability, overview. The enzyme might have an essential role in senescence- and differentiation-associated growth inhibition, involvement of hPNPase in producing pathological changes associated with aging by generating pro-inflammatory cytokines via reactive oxygen species and NF-kappaB, growth inhibition in different cancer cells and its molecular mechanism, overview. Direct involvement of PNPase in regulating specific cytosolic RNA import into the mitochondrial matrix, independently of its RNA-processing function
additional information
-
human melanoma cells infected with an adenovirus expressing hPNPaseold-35 and are used for identification of miRNAs differentially and specifically regulated by hPNPaseold-35. Overexpression of miR-221 in HO-1 cells confers resistance to IFN-beta-mediated growth arrest
additional information
the C-terminal S1 domain is not critical for RNA binding, and conversely, the conserved GXXG motif in the KH domain directly participates in RNA binding in hPNPase. The enzyme uses a KH pore to trap a long RNA 3' tail that is further delivered into an RNase PH channel for the degradation process. The three KH domains form a KH pore situated on the top of the hexameric ring-like structure. The KH pore extends the central channel formed by the RNase PH domains and is involved in the binding of RNA substrates, which are further delivered to the active site located within the central channel. Structural RNA with short 3' tails are, on the other hand, transported but not digested by hPNPase. Structural model of hPNPase, overview
additional information
-
the C-terminal S1 domain is not critical for RNA binding, and conversely, the conserved GXXG motif in the KH domain directly participates in RNA binding in hPNPase. The enzyme uses a KH pore to trap a long RNA 3' tail that is further delivered into an RNase PH channel for the degradation process. The three KH domains form a KH pore situated on the top of the hexameric ring-like structure. The KH pore extends the central channel formed by the RNase PH domains and is involved in the binding of RNA substrates, which are further delivered to the active site located within the central channel. Structural RNA with short 3' tails are, on the other hand, transported but not digested by hPNPase. Structural model of hPNPase, overview
additional information
-
two conserved catalytic RNase PH regions, a small domain of about 250 amino acid residues involved primarily in the 3' processing of transfer RNA precursors, are present at the N-terminus of the human enzyme. The RNA-binding property of hPNPase is conferred by two C-terminal RNA-binding domains, KH and S1
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PNPT1_HUMAN
783
0
85951
Swiss-Prot
Mitochondrion (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
80900
3 * 80900, about, sequence calculation, the trimeric hPNPase has a hexameric ring-like structure formed by six RNase PH domains, capped with a trimeric KH pore, the enzyme has a conserved GXXG motif in the KH domain, structural model of hPNPase, overview
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
trimer
additional information
trimer
3 * 80900, about, sequence calculation, the trimeric hPNPase has a hexameric ring-like structure formed by six RNase PH domains, capped with a trimeric KH pore, the enzyme has a conserved GXXG motif in the KH domain, structural model of hPNPase, overview
additional information
enzyme interacts with AKT kinase coactivator TCL1. The AKT interaction domain on TCL1 binds either Rnase PH repeat domain on PNPase without influencing its RNA degrading activity
additional information
polyribonucleotide phosphorylase interacts with AKT kinase coactivator TCL1. The AKT interaction domain on TCL1 binds either polyribonucleotide phosphorylase PH repeat domain without influencing its RNA degrading activity, compatible with predicted docking models for a TCL1-PNPase complex
additional information
domain organization of full-length and S1 domain-truncated hPNPase. overview
additional information
-
domain organization of full-length and S1 domain-truncated hPNPase. overview
additional information
-
two conserved catalytic RNase PH regions, are present at the N-terminus of the enzyme
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
processing of the N-terminal targeting sequence upon import into mitochondria
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
homology modeling based on structure of Streptomyces antibioticus ortholog. Enzyme displays a doughnut-shaped trimer with a central channel to accommodate a single-stranded RNA molecule. The circular structure is composed of the first and second core domains, while the KH and S1 RNA binding domains are located at the top, adjacent to the gate entrance into the circle
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wild-type and S1 domain-truncated hPNPase, hanging-drop vapor diffusion method, mixxing of 0.001 ml of 10 mg/ml protein in 50 mM Tris, pH 8.0, and 150 mM NaCl, with 0.001 ml of reservoir solution containing 0.1 M citrate, pH 5.0, 10% v/v 2-propanol and 26% v/v PEG 400, room temperature, X-ray diffraction structure determination and analysis at 2.1 A resolution, molecular replacement method
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D135G
-
unlike trimeric wild-type, mutant is monomeric. Almost complete inhibition of degradation and polyadenylation activities
additional information
additional information
expression of polynucleotide phosphorylase mutants lacking specific functional domains, i.e., mitochondrial translocation signal (MTS), catalytic domains (RPH1 and RPH2) and RNA binding domains (KH and S1), in cultured HeLa cells. MTS is required for polynucleotide phosphorylase to reduce 8-hydrooxyguanosine in mitochondria, but not in cytoplasm. Both RPH1 or RPH2 domain alone are able to support the full activity of polynucleotide phosphorylase in reducing 8-hydrooxyguanosine during oxidative stress, and the S1 RNA-binding domain, but not KH, is required for polynucleotide phosphorylase to reduce 8-hydrooxyguanosine under oxidative stress
additional information
-
expression of polynucleotide phosphorylase mutants lacking specific functional domains, i.e., mitochondrial translocation signal (MTS), catalytic domains (RPH1 and RPH2) and RNA binding domains (KH and S1), in cultured HeLa cells. MTS is required for polynucleotide phosphorylase to reduce 8-hydrooxyguanosine in mitochondria, but not in cytoplasm. Both RPH1 or RPH2 domain alone are able to support the full activity of polynucleotide phosphorylase in reducing 8-hydrooxyguanosine during oxidative stress, and the S1 RNA-binding domain, but not KH, is required for polynucleotide phosphorylase to reduce 8-hydrooxyguanosine under oxidative stress
additional information
-
depletion of enzyme by RNAi approach or overexpression of c-myc protects melanoma cells from interferon-beta mediated grwoth inhibition. Targeted overexpression of enzyme as a therapeutic strategy for c-myc overexpressing and interferon-beta resisitant tumors
additional information
-
enzyme depletion using RNAi does not affect mitochondrial RNA levels but impairs mitochondrial electrochemical membrane potential, decreases respiratory chain activity and correlates with altered mitochondrial morphology. This results in F0F1-ATP synthase instability, impaired ATP generation, lactate accumulation, and AMP kinase phosphorylation with reduced cell proliferation
additional information
-
overexpression of polynucleotide phosphorylase in HeLa cells under oxidative stress conditions reduces RNA oxidation and increases cell viability against H2O2 insult. Knock-down of enzyme decreases viability and increases 8-oxoguanosine levels in cells exposed to H2O2
additional information
-
stable silencing by establishing HeLa cell lines expressing shRNA. Silencing significantly affects processing and polyadenylation of mitochondrial mRNAs with different effects on different genes. The stable poly(A) tails at the 3' ends of COX1 transcripts are abolished, while COX3 poly(A) tails remain unaffected and ND5 and ND3 poly(A) extensions increase in length. Despite the lack of polyadenylation at the 3' end, COX1 mRNA and protein accumulate to normal levels, as is the case for all 13 mitochondria-encoded proteins. ATP depletion also alters poly(A) tail length
additional information
-
the promoter of Progression Elevated Gene-3 functions selectively in a diverse array of human cancer cells. An adenovirus constructed with the Progression Elevated Gene-3 promoter driving expression of polyribonucleotide phosphorylase containing a C-terminal hemaglutinin-tag induces robust transgene expression, growth suppression, apoptosis, and cell-cycle arrest in a broad panel of pancreatic cancer cells
additional information
-
upon expression in Escherichia coli, human enzyme does not form hetero-complexes with Escheichia coli enzyme
additional information
generation of a S1 domain-lacking mutant enzyme, domain organization of full-length and S1 domain-truncated hPNPase. overview. Full-length and DELTAS1 hPNPase cleave the poly(A)12 and poly(U)12 RNA with similar activities and DELTAS1 hPNPase cleaves ssRNA substrate almost as efficiently as full-length PNPase
additional information
-
generation of a S1 domain-lacking mutant enzyme, domain organization of full-length and S1 domain-truncated hPNPase. overview. Full-length and DELTAS1 hPNPase cleave the poly(A)12 and poly(U)12 RNA with similar activities and DELTAS1 hPNPase cleaves ssRNA substrate almost as efficiently as full-length PNPase
additional information
-
human melanoma cells are infected with empty adenovirus or with an adenovirus expressing hPNPaseold-35 and identification of miRNAs differentially and specifically regulated by hPNPaseold-35
additional information
-
targeted overexpression of hPNPase represents a strategy to selectively downregulate RNA expression and consequently intervene in a variety of pathophysiological conditions, enzyme silencing in PNPase RNA interference-transfected HEK293 cells
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
MonoQ colmn chromatography, metal ion affinity chromatography, and Superdex 200 gel filtration
-
recombinant N-terminally His-tagged wild-type and mutant enzymes from Escherichia coli strain BL21-CodonPlus (DE3)-RIPL by nickel affinty chromatography and gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
ectopic expression of human polynucleotide phosphorylase, i.e. hPNPaseold-35, in human HO-1 melanoma cells results in growth suppression
enhanced expression of hPNPase(old-35) via a replication-incompetent adenovirus (Ad.hPNPase(old-35)) in human melanoma cells and normal melanocytes
-
expression of N-terminally His-tagged wild-type and mutant enzymes in Escherichia coli strain BL21-CodonPlus (DE3)-RIPL
gene cloning using an overlapping pathway screening strategy designed to identify genes coordinately regulated during the processes of cellular differentiation and senescence, overview. Expression in HO-1 cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
molecular biology
-
targeted overexpression of hPNPase represents a strategy to selectively downregulate RNA expression and consequently intervene in a variety of pathophysiological conditions
medicine
-
depletion of enzyme by RNAi approach or overexpression of c-myc protects melanoma cells from interferon-beta mediated grwoth inhibition. Targeted overexpression of enzyme as a therapeutic strategy for c-myc overexpressing and interferon-beta resistant tumors
medicine
-
the apoptosis-inducing activity of polynucleotide phosphorylase is mediated by activation of double-stranded RNA-dependent protein kinase. Activation of RNA-dependent protein kinase by polynucleotide phosphorylase precedes phosphorylation of eukaryotic initiation factor-2A and induction of growth arrest and DNA damage-inducible gene 153, GADD153, that culminates in the shutdown of protein synthesis and apoptosis. Activation of RNA-dependent protein kinase by polynucleotide phosphorylase also instigates down-regulation of the antiapoptotic protein Bcl-xL. A dominant-negative inhibitor of RNA-dependent protein kinase, as well as GADD153 antisense or bcl-xL overexpression, effectively inhibits apoptosis induction by polynucleotide phosphorylase
medicine
-
the promoter of Progression Elevated Gene-3 functions selectively in a diverse array of human cancer cells. An adenovirus constructed with the Progression Elevated Gene-3 promoter driving expression of polyribonucleotide phosphorylase containing a C-terminal hemaglutinin-tag induces robust transgene expression, growth suppression, apoptosis, and cell-cycle arrest in a broad panel of pancreatic cancer cells, with minimal effects in normal immortalized pancreatic cells. Expression correlates with arrest in the G2/M phase of the cell cycle and up-regulation of the cyclin-dependent kinase inhibitors p21CIP1/WAF-1/MDA-6 and p27KIP1. In a nude mouse xenograft model,construct injections effectively inhibit growth of human pancreatic cancer cells in vivo
medicine
-
targeted overexpression of hPNPaseold-35 might provide an effective therapeutic strategy for miR-221-overexpressing and IFN-resistant tumors, such as melanoma
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Godefroy-Colburn, T.; Grunenberg-Manago, M.
Polynucleotide phosphorylase
The Enzymes, 3rd. Ed. (Boyer, P. D. , ed. )
7
533-574
1972
Ascaris lumbricoides, Auxenochlorella pyrenoidosa, Cavia porcellus, Escherichia coli, Halobacterium salinarum, Homo sapiens, Lactiplantibacillus plantarum, Micrococcus luteus, Neisseria meningitidis, Pseudomonas aeruginosa, Rattus norvegicus, Salmonella enterica subsp. enterica serovar Typhimurium, Spinacia oleracea, Synechococcus elongatus PCC 7942 = FACHB-805, Triticum aestivum
-
Leszczyniecka, M.; Kang, D.C.; Sarkar, D.; Su, Z.Z.; Holmes, M.; Valerie, K.; Fisher, P.B.
Identification and cloning of human polynucleotide phosphorylase, hPNPase old-35, in the context of terminal differentiation and cellular senescence
Proc. Natl. Acad. Sci. USA
99
16636-16641
2002
Homo sapiens (Q8TCS8), Homo sapiens
Sarkar, D.; Lebedeva, I.V.; Emdad, L.; Kang, D.C.; Baldwin, A.S.; Fisher, P.B.
Human polynucleotide phosphorylase (hPNPaseold-35): a potential link between aging and inflammation
Cancer Res.
64
7473-7478
2004
Homo sapiens
Nagaike, T.; Suzuki, T.; Katoh, T.; Ueda, T.
Human mitochondrial mRNAs are stabilized with polyadenylation regulated by mitochondria-specific poly(A) polymerase and polynucleotide phosphorylase
J. Biol. Chem.
280
19721-19727
2005
Homo sapiens
Hayakawa, H.; Sekiguchi, M.
Human polynucleotide phosphorylase protein in response to oxidative stress
Biochemistry
45
6749-6755
2006
Homo sapiens
French, S.W.; Dawson, D.W.; Chen, H.; Rainey, R.N.; Sievers, S.A.; Balatoni, C.E.; Wong, L.; Troke, J.J.; Nguyen, M.T.; Koehler, C.M.; Teitell, M.A.
The TCL1 oncoprotein binds the RNase PH domains of the PNPase exoribonuclease without affecting its RNA degrading activity
Cancer Lett.
248
198-210
2007
Homo sapiens (Q8TCS8)
Sarkar, D.; Park, E.S.; Fisher, P.B.
Defining the mechanism by which IFN-beta dowregulates c-myc expression in human melanoma cells: pivotal role for human polynucleotide phosphorylase (hPNPaseold-35)
Cell Death Differ.
13
1541-1553
2006
Homo sapiens
Chen, H.W.; Rainey, R.N.; Balatoni, C.E.; Dawson, D.W.; Troke, J.J.; Wasiak, S.; Hong, J.S.; McBride, H.M.; Koehler, C.M.; Teitell, M.A.; French, S.W.
Mammalian polynucleotide phosphorylase is an intermembrane space RNase that maintains mitochondrial homeostasis
Mol. Cell. Biol.
26
8475-8487
2006
Homo sapiens
Wu, J.; Li, Z.
Human polynucleotide phosphorylase reduces oxidative RNA damage and protects HeLa cell against oxidative stress
Biochem. Biophys. Res. Commun.
372
288-292
2008
Homo sapiens
Sarkar, D.; Park, E.S.; Barber, G.N.; Fisher, P.B.
Activation of double-stranded RNA dependent protein kinase, a new pathway by which human polynucleotide phosphorylase (hPNPase(old-35)) induces apoptosis
Cancer Res.
67
7948-7953
2007
Homo sapiens
Chan, I.; Lebedeva, I.V.; Su, Z.Z.; Sarkar, D.; Valerie, K.; Fisher, P.B.
Progression elevated gene-3 promoter (PEG-Prom) confers cancer cell selectivity to human polynucleotide phosphorylase (hPNPase(old-35))-mediated growth suppression
J. Cell. Physiol.
215
401-409
2008
Homo sapiens
Portnoy, V.; Palnizky, G.; Yehudai-Resheff, S.; Glaser, F.; Schuster, G.
Analysis of the human polynucleotide phosphorylase (PNPase) reveals differences in RNA binding and response to phosphate compared to its bacterial and chloroplast counterparts
RNA
14
297-309
2008
Homo sapiens
Slomovic, S.; Schuster, G.
Stable PNPase RNAi silencing: its effect on the processing and adenylation of human mitochondrial RNA
RNA
14
310-323
2008
Homo sapiens
Wang, D.D.; Shu, Z.; Lieser, S.A.; Chen, P.L.; Lee, W.H.
Human mitochondrial SUV3 and polynucleotide phosphorylase form a 330-kDa heteropentamer to cooperatively degrade double-stranded RNA with a 3'-to-5' directionality
J. Biol. Chem.
284
20812-20821
2009
Homo sapiens
Lin, C.L.; Wang, Y.T.; Yang, W.Z.; Hsiao, Y.Y.; Yuan, H.S.
Crystal structure of human polynucleotide phosphorylase: insights into its domain function in RNA binding and degradation
Nucleic Acids Res.
40
4146-4157
2012
Homo sapiens (G8TCS8), Homo sapiens
Das, S.K.; Bhutia, S.K.; Sokhi, U.K.; Dash, R.; Azab, B.; Sarkar, D.; Fisher, P.B.
Human polynucleotide phosphorylase (hPNPase(old-35)): an evolutionary conserved gene with an expanding repertoire of RNA degradation functions
Oncogene
30
1733-1743
2011
Homo sapiens, Mus musculus
Das, S.K.; Sokhi, U.K.; Bhutia, S.K.; Azab, B.; Su, Z.Z.; Sarkar, D.; Fisher, P.B.
Human polynucleotide phosphorylase selectively and preferentially degrades microRNA-221 in human melanoma cells
Proc. Natl. Acad. Sci. USA
107
11948-11953
2010
Homo sapiens
Malla, S.; Li, Z.
Functions of conserved domains of human polynucleotide phosphorylase on RNA oxidation
Insights Biomed. Res.
3
62-67
2019
Homo sapiens (Q8TCS8), Homo sapiens
Shepherd, D.L.; Hathaway, Q.A.; Pinti, M.V.; Nichols, C.E.; Durr, A.J.; Sreekumar, S.; Hughes, K.M.; Stine, S.M.; Martinez, I.; Hollander, J.M.
Exploring the mitochondrial microRNA import pathway through polynucleotide phosphorylase (PNPase)
J. Mol. Cell. Cardiol.
110
15-25
2017
Mus musculus (Q8K1R3), Mus musculus, Homo sapiens (Q8TCS8), Homo sapiens
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