Polynucleotide phosphorylase

Polynucleotide Phosphorylase

Structure of the PNPase trimer from Streptomyces antibioticus. PDB 1e3p.[1]
Identifiers
EC number 2.7.7.8
CAS number 9014-12-4
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

Polynucleotide Phosphorylase (PNPase) is a bifunctional enzyme with a phosphorolytic 3' to 5' exoribonuclease activity and a 3'-terminal oligonucleotide polymerase activity.[2] That is, it dismantles the RNA chain starting at the 3' end and working toward the 5' end.[1] It also synthesizes long, highly heteropolymeric tails in vivo. It accounts for all of the observed residual polyadenylation in strains of Escherichia coli missing the normal polyadenylation enzyme.[1] Discovered by Marianne Granburg Manago working in Severo Ochoa's lab in 1951, the RNA-polymerization activity of PNPase was initially believed to be responsible for DNA-dependent synthesis of messenger RNA, a notion that got disproved by the late.[3]

It is involved on mRNA processing and degradation in bacteria, plants,[4] and in humans.[5]

In humans, the enzyme is encoded by the PNPT1 gene. In its active form, the protein forms a ring structure consisting of three PNPase molecules. Each PNPase molecule consists of two RNase PH domains, an S1 RNA binding domain and a K-homology domain. The protein is present in bacteria and in the chloroplasts[2] and mitochondria[6] of some eukaryotic cells. In eukaryotes and archaea, a structurally and evolutionary related complex exists, called the exosome.[6]

The same abbreviation (PNPase) is also used for another, otherwise unrelated enzyme, Purine nucleoside phosphorylase.

Model organisms

Model organisms have been used in the study of PNPT1 function. A conditional knockout mouse line, called Pnpt1tm1a(KOMP)Wtsi[11][12] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[13][14][15]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[9][16] Twenty six tests were carried out on mutant mice and two significant abnormalities were observed.[9] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these animals.[9]

Human PNPase I
Identifiers
Symbol PNPASE
Alt. symbols PNPase, OLD35, old-35
Entrez 87178
HUGO 23166
OMIM 610316
PDB 1E3P
RefSeq NM_033109
UniProt Q8TCS8
Other data
EC number 2.7.7.8
Locus Chr. 2 p15

References

  1. 1 2 3 Symmons MF, Jones GH, Luisi BF (November 2000). "A duplicated fold is the structural basis for polynucleotide phosphorylase catalytic activity, processivity, and regulation". Structure. 8 (11): 1215–26. doi:10.1016/S0969-2126(00)00521-9. PMID 11080643.
  2. 1 2 Yehudai-Resheff S, Hirsh M, Schuster G (August 2001). "Polynucleotide phosphorylase functions as both an exonuclease and a poly(A) polymerase in spinach chloroplasts". Mol. Cell. Biol. 21 (16): 5408–16. doi:10.1128/MCB.21.16.5408-5416.2001. PMC 87263Freely accessible. PMID 11463823.
  3. ↑ Furth JJ, Hurwitz J, Anders M (1962). "The role of deoxyribonucleic acid in ribonucleic acid synthesis. I. The purification and properties of ribonucleic acid polymerase" (PDF). The Journal of Biological Chemistry. 237: 2611–9. PMID 13895983.
  4. ↑ Yehudai-Resheff S, Zimmer SL, Komine Y, Stern DB (March 2007). "Integration of chloroplast nucleic acid metabolism into the phosphate deprivation response in Chlamydomonas reinhardtii". Plant Cell. 19 (3): 1023–38. doi:10.1105/tpc.106.045427. PMC 1867357Freely accessible. PMID 17351118.
  5. ↑ Sarkar D, Fisher PB (May 2006). "Human polynucleotide phosphorylase (hPNPase old-35): an RNA degradation enzyme with pleiotrophic biological effects" (PDF). Cell Cycle. 5 (10): 1080–4. doi:10.4161/cc.5.10.2741. PMID 16687933.
  6. 1 2 Schilders G, van Dijk E, Raijmakers R, Pruijn GJ (2006). "Cell and molecular biology of the exosome: how to make or break an RNA". Int. Rev. Cytol. 251: 159–208. doi:10.1016/S0074-7696(06)51005-8. PMID 16939780.
  7. ↑ "Salmonella infection data for Pnpt1". Wellcome Trust Sanger Institute.
  8. ↑ "Citrobacter infection data for Pnpt1". Wellcome Trust Sanger Institute.
  9. 1 2 3 4 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  10. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  11. ↑ "International Knockout Mouse Consortium".
  12. ↑ "Mouse Genome Informatics".
  13. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410Freely accessible. PMID 21677750.
  14. ↑ Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  15. ↑ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  16. ↑ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837Freely accessible. PMID 21722353.
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