The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

PNPT1  -  polyribonucleotide nucleotidyltransferase 1

Homo sapiens

Synonyms: 3'-5' RNA exonuclease OLD35, COXPD13, DFNB70, OLD35, PNPASE, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of PNPT1

  • Overexpression of hPNPase(OLD-35) in human melanoma cells and melanocytes induces distinctive changes associated with senescence, potentially mediated by direct degradation of c-myc mRNA by this enzyme. hPNPase(OLD-35) contains two RNase PH (RPH) domains, one PNPase domain, and two RNA binding domains [1].
  • These results suggest that there is no enzyme similar to E. coli PAP I in spinach chloroplasts and that polyadenylation and exonucleolytic degradation of RNA in spinach chloroplasts are performed by one enzyme, PNPase [2].
  • Our findings suggest that PNPase plays multifaceted roles in enhancing Yersinia survival in response to stressful conditions [3].
  • Interferon-alpha (IFN-alpha) enhances the activity of the 5-fluorouracil (5-FU) prodrug 5'-deoxy-5-fluorouridine (5'-dFUrd) in colorectal cancer cells in vitro by upregulating the enzyme pyrimidine nucleoside phosphorylase (PNPase), which is responsible for converting 5'-dFUrd to 5-FU [4].
  • Pnpt, the natural promoter driving expression of the kanamycin-resistance determinant from Tn5, was poorly expressed in Anabaena [5].

High impact information on PNPT1


Biological context of PNPT1


Anatomical context of PNPT1

  • Here, we demonstrate that the hPNPase is localized in mitochondria [11].
  • Polynucleotide phosphorylase (PNPase) is an exoribonuclease and poly(A) polymerase postulated to function in the cytosol and mitochondrial matrix [8].
  • PNPase is required for the optimal functioning of the Yersinia type three secretion system (TTSS), an organelle that injects effector proteins directly into host cells [3].
  • Here, we show that PNPase also enhances the ability of Yersinia pseudotuberculosis and Yersinia pestis to withstand the killing activities of murine macrophages [3].
  • The most potent inhibitor of human erythrocyte PNPase, [[[5-(2-amino-1,6-dihydro-6-oxo-9H-purin-9- yl)pentyl]phosphinico]methyl]phosphonic acid (2b), was a multisubstrate analogue inhibitor with a Ki' of 3.1 nM [12].

Associations of PNPT1 with chemical compounds

  • The mutation responsible (pnp-71 ) has substituted a highly conserved glycine residue in the KH domain of PNPase with aspartate [10].
  • These inhibitors displayed competitive kinetics with respect to inosine and inorganic phosphate, which showed that these compounds possess binding determinants for both the purine- and phosphate-binding domains of the enzyme, characteristics that are consistent with 3f and 3j being multisubstrate analogue inhibitors of PNPase [13].
  • An initial set of six analogues of the weak PNPase inhibitor 9-benzylguanine (2) contained a phosphonic acid group linked to the ortho, meta, or para position of the aryl moiety via two- or three-atom spacers [13].
  • The amine-phosphate interaction also served to confirm that a quinazolin-4(3H)-one binds in the PNPase active sites like a purine substrate [14].
  • The reaction of 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole [NBD-Cl] with purified eel electrophax Na+ and K+ stimulated adenosine triphosphatase [(Na-K)ATPase] has been monitored by changes in the (Na-K)ATPase activity, the K+ stimulated p-nitrophenyl phosphatase [PNPase] activity, and the protein ultraviolet absorption spectrum [15].

Physical interactions of PNPT1

  • We conclude from these studies that PNPase is the RNA-binding cofactor for this poly(A) polymerase and is an integral player in the reaction catalyzed by this enzyme [16].

Other interactions of PNPT1


Analytical, diagnostic and therapeutic context of PNPT1

  • Electron microscopy shows the exosome to resemble PNPase but with key differences likely related to the position of RNA binding domains, and to the location of domains unique to the exosome [21].
  • HPLC is highly suitable for PNPase as both the forward and reverse reactions can be monitored [22].
  • Hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) and purine nucleoside phosphorylase (PNPase) activities were simultaneously determined in erythrocyte lysates, using the reversed-phase mode of high-performance liquid chromatography [19].
  • CI-972 (2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2- d]pyrimidin-4-one monohydrochloride, monohydrate) is a competitive inhibitor of PNPase (E.C., Ki = 0.83 microM) entering clinical trials as a T cell-selective immunosuppressive agent [23].
  • In this work, we performed a systematic PCR mutagenesis of discrete pnp regions and screened the mutants for diverse phenotypic traits affected by PNPase [20].


  1. Defining the domains of human polynucleotide phosphorylase (hPNPaseOLD-35) mediating cellular senescence. Sarkar, D., Park, E.S., Emdad, L., Randolph, A., Valerie, K., Fisher, P.B. Mol. Cell. Biol. (2005) [Pubmed]
  2. Polynucleotide phosphorylase functions as both an exonuclease and a poly(A) polymerase in spinach chloroplasts. Yehudai-Resheff, S., Hirsh, M., Schuster, G. Mol. Cell. Biol. (2001) [Pubmed]
  3. Modulation of yersinia type three secretion system by the S1 domain of polynucleotide phosphorylase. Rosenzweig, J.A., Weltman, G., Plano, G.V., Schesser, K. J. Biol. Chem. (2005) [Pubmed]
  4. Interferon alpha and 5'-deoxy-5-fluorouridine in colon cancer: effects as single agents and in combination on growth of xenograft tumours. Laurent, P.L., Tevaearai, H.T., Eliason, J.F., Givel, J.C., Odartchenko, N. Eur. J. Cancer (1994) [Pubmed]
  5. Strong and regulated promoters in the cyanobacterium Anabaena PCC 7120. Elhai, J. FEMS Microbiol. Lett. (1993) [Pubmed]
  6. Messenger RNA stability and its role in control of gene expression in bacteria and phages. Grunberg-Manago, M. Annu. Rev. Genet. (1999) [Pubmed]
  7. Identification and cloning of human polynucleotide phosphorylase, hPNPase old-35, in the context of terminal differentiation and cellular senescence. Leszczyniecka, M., Kang, D.C., Sarkar, D., Su, Z.Z., Holmes, M., Valerie, K., Fisher, P.B. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  8. A New Function in Translocation for the Mitochondrial i-AAA Protease Yme1: Import of Polynucleotide Phosphorylase into the Intermembrane Space. Rainey, R.N., Glavin, J.D., Chen, H.W., French, S.W., Teitell, M.A., Koehler, C.M. Mol. Cell. Biol. (2006) [Pubmed]
  9. Mammalian Polynucleotide Phosphorylase Is an Intermembrane Space RNase That Maintains Mitochondrial Homeostasis. 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. Mol. Cell. Biol. (2006) [Pubmed]
  10. A novel mutation in the KH domain of polynucleotide phosphorylase affects autoregulation and mRNA decay in Escherichia coli. García-Mena, J., Das, A., Sánchez-Trujillo, A., Portier, C., Montañez, C. Mol. Microbiol. (1999) [Pubmed]
  11. Human polynucleotide phosphorylase, hPNPase, is localized in mitochondria. Piwowarski, J., Grzechnik, P., Dziembowski, A., Dmochowska, A., Minczuk, M., Stepien, P.P. J. Mol. Biol. (2003) [Pubmed]
  12. [[(Guaninylalkyl)phosphinico]methyl]phosphonic acids. Multisubstrate analogue inhibitors of human erythrocyte purine nucleoside phosphorylase. Kelley, J.L., McLean, E.W., Crouch, R.C., Averett, D.R., Tuttle, J.V. J. Med. Chem. (1995) [Pubmed]
  13. 9-[(Phosphonoalkyl)benzyl]guanines. Multisubstrate analogue inhibitors of human erythrocyte purine nucleoside phosphorylase. Kelley, J.L., Linn, J.A., McLean, E.W., Tuttle, J.V. J. Med. Chem. (1993) [Pubmed]
  14. Rational design of quinazoline-based irreversible inhibitors of human erythrocyte purine nucleoside phosphorylase. Dempcy, R.O., Skibo, E.B. Biochemistry (1991) [Pubmed]
  15. Reaction of (Na-K)ATPase with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole: evidence for an essential tyrosine at the active site. Cantley, L.C., Gelles, J., Josephson, L. Biochemistry (1978) [Pubmed]
  16. Polynucleotide phosphorylase is a component of a novel plant poly(A) polymerase. Li, Q.S., Gupta, J.D., Hunt, A.G. J. Biol. Chem. (1998) [Pubmed]
  17. Blood lymphocytes in chronic lymphocytic leukaemia and Hodgkin's disease: Immunological features and enzymes of nucleoside metabolism. Ambrogi, F., Grassi, B., Ronca-Testoni, S., Ronca, G. Clin. Exp. Immunol. (1977) [Pubmed]
  18. Guanine, pyrazolo[3,4-d]pyrimidine, and triazolo[4,5-d]pyrimidine (8-azaguanine) phosphonate acyclic derivatives as inhibitors of purine nucleoside phosphorylase. Beauchamp, L.M., Tuttle, J.V., Rodriguez, M.E., Sznaidman, M.L. J. Med. Chem. (1996) [Pubmed]
  19. Simultaneous high-performance liquid chromatographic assay of the activities of erythrocytic hypoxanthine-guanine phosphoribosyl transferase and purine nucleoside phosphorylase. Halfpenny, A.P., Brown, P.R. J. Chromatogr. (1985) [Pubmed]
  20. Genetic analysis of polynucleotide phosphorylase structure and functions. Briani, F., Del Favero, M., Capizzuto, R., Consonni, C., Zangrossi, S., Greco, C., De Gioia, L., Tortora, P., Deh??, G. Biochimie (2007) [Pubmed]
  21. A complex prediction: three-dimensional model of the yeast exosome. Aloy, P., Ciccarelli, F.D., Leutwein, C., Gavin, A.C., Superti-Furga, G., Bork, P., Bottcher, B., Russell, R.B. EMBO Rep. (2002) [Pubmed]
  22. Optimized assay for purine nucleoside phosphorylase by reversed-phase high-performance liquid chromatography. Halfpenny, A.P., Brown, P.R. J. Chromatogr. (1980) [Pubmed]
  23. Selective in vitro inhibition of human MOLT-4 T lymphoblasts by the novel purine nucleoside phosphorylase inhibitor, CI-972. Gilbertsen, R.B., Dong, M.K., Kossarek, L.M., Sircar, J.C., Kostlan, C.R., Conroy, M.C. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
WikiGenes - Universities