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Polyribonucleotide nucleotidyltransferase 1, mitochondrial

 
Known also as: 3'-5' RNA exonuclease OLD35, PNPase old-35, Polynucleotide phosphorylase 1, Polynucleotide phosphorylase-like protein

Known abbreviations: PNPase 1, PNPT1

FUNCTION:

RNA-binding protein implicated in numerous RNA metabolic processes. Hydrolyzes single-stranded polyribonucleotides processively in the 3'-to-5' direction. Mitochondrial intermembrane factor with RNA-processing exoribonulease activity. Component of the mitochondrial degradosome (mtEXO) complex, that degrades 3' overhang double-stranded RNA with a 3'-to-5' directionality in an ATP-dependent manner. Required for correct processing and polyadenylation of mitochondrial mRNAs. Plays a role as a cytoplasmic RNA import factor that mediates the translocation of small RNA components, like the 5S RNA, the RNA subunit of ribonuclease P and the mitochondrial RNA-processing (MRP) RNA, into the mitochondrial matrix. Plays a role in mitochondrial morphogenesis and respiration; regulates the expression of the electron transport chain (ETC) components at the mRNA and protein levels. In the cytoplasm, shows a 3'-to-5' exoribonuclease mediating mRNA degradation activity; degrades c-myc mRNA upon treatment with IFNB1/IFN-beta, resulting in a growth arrest in melanoma cells. Regulates the stability of specific mature miRNAs in melanoma cells; specifically and selectively degrades miR-221, preferentially. Plays also a role in RNA cell surveillance by cleaning up oxidized RNAs. Binds to the RNA subunit of ribonuclease P, MRP RNA and miR-221 microRNA.

CATALYTIC ACTIVITY:

RNA(n+1) + phosphate = RNA(n) + a nucleoside diphosphate.

SUBUNIT STRUCTURE:

Homotrimer; in free form. Homooligomer. Component of the mitochondrial degradosome (mtEXO) complex which is a heteropentamer containing 2 copies of SUPV3L1 and 3 copies of PNPT1. Interacts with TCL1A; the interaction has no effect on PNPT1 exonuclease activity.

CELLULAR LOCALIZATION:

Cytoplasm. Mitochondrion. Mitochondrion intermembrane space; Peripheral membrane protein.

INDUCTION:

Up-regulated in cells upon senescence and terminal differentiation. Up-regulated after treatment with IFNB1/IFN-beta.

POST-TRANSLATIONAL MODIFICATION:

Phosphorylated upon DNA damage, probably by ATM or ATR.



NCBI GI number(s): 188528628
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot Q8TCS8 Q8TCS8
BRENDA - -
KEGG - -
PFAM: - Q8TCS8 (Link - using uniprot id)
InterPro: - Q8TCS8 (Link - using uniprot id)
CATH: - -
SCOP: - -
Solved crystal structures: 3U1K
[PDB] [details]


Protein sequence:
MAACRYCCSCLRLRPLSDGPFLLPRRDRALTQLQVRALWSSAGSRAVAVD
LGNRKLEISSGKLARFADGSAVVQSGDTAVMVTAVSKTKPSPSQFMPLVV
DYRQKAAAAGRIPTNYLRREIGTSDKEILTSRIIDRSIRPLFPAGYFYDT
QVLCNLLAVDGVNEPDVLAINGASVALSLSDIPWNGPVGAVRIGIIDGEY
VVNPTRKEMSSSTLNLVVAGAPKSQIVMLEASAENILQQDFCHAIKVGVK
YTQQIIQGIQQLVKETGVTKRTPQKLFTPSPEIVKYTHKLAMERLYAVFT
DYEHDKVSRDEAVNKIRLDTEEQLKEKFPEADPYEIIESFNVVAKEVFRS
IVLNEYKRCDGRDLTSLRNVSCEVDMFKTLHGSALFQRGQTQVLCTVTFD
SLESGIKSDQVITAINGIKDKNFMLHYEFPPYATNEIGKVTGLNRRELGH
GALAEKALYPVIPRDFPFTIRVTSEVLESNGSSSMASACGGSLALMDSGV
PISSAVAGVAIGLVTKTDPEKGEIEDYRLLTDILGIEDYNGDMDFKIAGT
NKGITALQADIKLPGIPIKIVMEAIQQASVAKKEILQIMNKTISKPRASR
KENGPVVETVQVPLSKRAKFVGPGGYNLKKLQAETGVTISQVDEETFSVF
APTPSAMHEARDFITEICKDDQEQQLEFGAVYTATITEIRDTGVMVKLYP
NMTAVLLHNTQLDQRKIKHPTALGLEVGQEIQVKYFGRDPADGRMRLSRK
VLQSPATTVVRTLNDRSSIVMGEPISQSSSNSQ

Polyribonucleotide nucleotidyltransferase 1, mitochondrial (Homo sapiens) is product of expression of POLYRIBONUCLEOTIDE NUCLEOTIDYLTRANSFERASE 1 gene.

Polyribonucleotide nucleotidyltransferase 1, mitochondrial (Homo sapiens) belongs to following protein families:
References:

Title Authors Journal Publication date (Issue) PubMed ID
Protein-protein interactions between human exosome components support the assembly of RNase PH-type subunits into a six-membered PNPase-like ring. Raijmakers R, Egberts WV, van Venrooij WJ, Pruijn GJ J Mol Biol 2002-11-01 (323) 12419256
Human polynucleotide phosphorylase reduces oxidative RNA damage and protects HeLa cell against oxidative stress. Wu J, Li Z Biochem Biophys Res Commun 2008-07-25 (372) 18501193
Analysis of the human polynucleotide phosphorylase (PNPase) reveals differences in RNA binding and response to phosphate compared to its bacterial and chloroplast counterparts. Portnoy V, Palnizky G, Yehudai-Resheff S, Glaser F, Schuster G RNA 2008-01-01 (14) 18083836
The TCL1 oncoprotein binds the RNase PH domains of the PNPase exoribonuclease without affecting its RNA degrading activity. French SW, Dawson DW, Chen HW, Rainey RN, Sievers SA, Balatoni CE, Wong L, Troke JJ, Nguyen MT, Koehler CM, Teitell MA Cancer Lett 2007-04-18 (248) 16934922
Mammalian polynucleotide phosphorylase is an intermembrane space RNase that maintains mitochondrial homeostasis. Chen HW, Rainey RN, Balatoni CE, Dawson DW, Troke JJ, Wasiak S, Hong JS, McBride HM, Koehler CM, Teitell MA, French SW Mol Cell Biol 2006-11-01 (26) 16966381
Human polynucleotide phosphorylase: location matters. Chen HW, Koehler CM, Teitell MA Trends Cell Biol 2007-12-01 (17) 17983748
Stable PNPase RNAi silencing: its effect on the processing and adenylation of human mitochondrial RNA. Slomovic S, Schuster G RNA 2008-01-01 (14) 18083837
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, K Genome Res 2004-10-01 (14) 15489334
Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M Nature 2005-04-07 (434) 15815621
Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S Anal Chem 2009-06-01 (81) 19413330
Initial characterization of the human central proteome. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J BMC Syst Biol 2011-01-01 (5) 21269460
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ Science 2007-05-25 (316) 17525332
The full-ORF clone resource of the German cDNA Consortium. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I BMC Genomics 2007-01-01 (8) 17974005
Lysine acetylation targets protein complexes and co-regulates major cellular functions. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M Science 2009-08-14 (325) 19608861
Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra. Yu LR, Zhu Z, Chan KC, Issaq HJ, Dimitrov DS, Veenstra TD J Proteome Res 2007-11-01 (6) 17924679
Identification and cloning of human polynucleotide phosphorylase, hPNPase old-35, in the context of terminal differentiation and cellular senescence. Leszczyniecka M, Kang DC, Sarkar D, Su ZZ, Holmes M, Valerie K, Fisher PB Proc Natl Acad Sci U S A 2002-12-24 (99) 12473748
Down-regulation of Myc as a potential target for growth arrest induced by human polynucleotide phosphorylase (hPNPaseold-35) in human melanoma cells. Sarkar D, Leszczyniecka M, Kang DC, Lebedeva IV, Valerie K, Dhar S, Pandita TK, Fisher PB J Biol Chem 2003-07-04 (278) 12721301
Human polynucleotide phosphorylase, hPNPase, is localized in mitochondria. Piwowarski J, Grzechnik P, Dziembowski A, Dmochowska A, Minczuk M, Stepien PP J Mol Biol 2003-06-20 (329) 12798676
Defining the domains of human polynucleotide phosphorylase (hPNPaseOLD-35) mediating cellular senescence. Sarkar D, Park ES, Emdad L, Randolph A, Valerie K, Fisher PB Mol Cell Biol 2005-08-01 (25) 16055741
Defining the mechanism by which IFN-beta dowregulates c-myc expression in human melanoma cells: pivotal role for human polynucleotide phosphorylase (hPNPaseold-35). Sarkar D, Park ES, Fisher PB Cell Death Differ 2006-09-01 (13) 16410805
Human mitochondrial SUV3 and polynucleotide phosphorylase form a 330-kDa heteropentamer to cooperatively degrade double-stranded RNA with a 3'-to-5' directionality. Wang DD, Shu Z, Lieser SA, Chen PL, Lee WH J Biol Chem 2009-07-31 (284) 19509288
PNPASE regulates RNA import into mitochondria. Wang G, Chen HW, Oktay Y, Zhang J, Allen EL, Smith GM, Fan KC, Hong JS, French SW, McCaffery JM, Lightowlers RN, Morse HC 3rd, Koehler CM, Teitell MA Cell 2010-08-06 (142) 20691904
Human polynucleotide phosphorylase selectively and preferentially degrades microRNA-221 in human melanoma cells. Das SK, Sokhi UK, Bhutia SK, Azab B, Su ZZ, Sarkar D, Fisher PB Proc Natl Acad Sci U S A 2010-06-01 (107) 20547861



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Last modification of this entry: 2012-07-05 14:44:00
Edited by a user: kaja
Edited content: Changed publications.

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