Protein-coding gene in the species Homo sapiens
Poly(A) polymerase alpha is an enzyme that in humans is encoded by the PAPOLA gene .[5] [6] [7]
PAPOLA binds to FIP1L1 (Factor interacting with PAPOLA and CPSF1), a subunit of the cleavage and polyadenylation specificity factor subunit 1 (CPSF1) complex. This complex polyadenylates the 3' end of precursor mRNAs (pre-mRNA) (see CPSF ). CPSF1 is an RNA processing protein that binds to uracil -rich sequences in pre-mRNA, binds with and stimulates PAPOLA's Polynucleotide adenylyltransferase activity, and thereby adds adenylyl residues to pre-mRNA. This poly-adenylyl action increases pre mRNA's maturation and movement from the nucleus to cytoplasm while dramatically increasing the stability of the mRNA formed from pre-mRNA: FIP1L1 is a Pre-mRNA 3'-end-processing factor. FIP1L1 gene fusions between it and either the platelet-derived growth factor receptor, alpha (PGDFRA ) or Retinoic acid receptor alpha (RARA) genes are causes of certain human diseases associated with pathologically increased levels of blood eosinophils and/or Leukemias .[8]
References [ edit ] ^ a b c GRCh38: Ensembl release 89: ENSG00000090060 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021111 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ Thuresson AC, Astrom J, Astrom A, Gronvik KO, Virtanen A (Mar 1994). "Multiple forms of poly(A) polymerases in human cells" . Proc Natl Acad Sci U S A . 91 (3): 979–83. Bibcode :1994PNAS...91..979T . doi :10.1073/pnas.91.3.979 PMC 521437 PMID 8302877 . ^ Yamauchi T, Sugimoto J, Hatakeyama T, Asakawa S, Shimizu N, Isobe M (Sep 1999). "Assignment of the human poly(A) polymerase (PAP) gene to chromosome 14q32.1-q32.2 and isolation of a polymorphic CA repeat sequence" . J Hum Genet . 44 (4): 253–5. doi :10.1007/s100380050154 PMID 10429366 . ^ "Entrez Gene: PAPOLA poly(A) polymerase alpha" .^ "FIP1L1 factor interacting with PAPOLA and CPSF1 [Homo sapiens (Human)] - Gene - NCBI" . Further reading [ edit ] Pendurthi UR, Alok D, Rao LV (1997). "Binding of factor VIIa to tissue factor induces alterations in gene expression in human fibroblast cells: up-regulation of poly(A) polymerase" . Proc. Natl. Acad. Sci. U.S.A . 94 (23): 12598–603. Bibcode :1997PNAS...9412598P . doi :10.1073/pnas.94.23.12598 PMC 25051 PMID 9356495 . Varani L, Gunderson SI, Mattaj IW, et al. (2000). "The NMR structure of the 38 kDa U1A protein - PIE RNA complex reveals the basis of cooperativity in regulation of polyadenylation by human U1A protein". Nat. Struct. Biol . 7 (4): 329–35. doi :10.1038/74101 . PMID 10742179 . S2CID 13432764 . Mouland AJ, Coady M, Yao XJ, Cohen EA (2002). "Hypophosphorylation of poly(A) polymerase and increased polyadenylation activity are associated with human immunodeficiency virus type 1 Vpr expression" . Virology . 292 (2): 321–30. doi :10.1006/viro.2001.1261 PMID 11878934 . Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences" . Proc. Natl. Acad. Sci. U.S.A . 99 (26): 16899–903. Bibcode :2002PNAS...9916899M . doi :10.1073/pnas.242603899 PMC 139241 PMID 12477932 . Kim H, Lee JH, Lee Y (2003). "Regulation of poly(A) polymerase by 14-3-3epsilon" . EMBO J . 22 (19): 5208–19. doi :10.1093/emboj/cdg486 . PMC 204469 PMID 14517258 . Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs" . Nat. Genet . 36 (1): 40–5. doi :10.1038/ng1285 PMID 14702039 . Bouwmeester T, Bauch A, Ruffner H, et al. (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol . 6 (2): 97–105. doi :10.1038/ncb1086 . PMID 14743216 . S2CID 11683986 . Kaufmann I, Martin G, Friedlein A, et al. (2005). "Human Fip1 is a subunit of CPSF that binds to U-rich RNA elements and stimulates poly(A) polymerase" . EMBO J . 23 (3): 616–26. doi :10.1038/sj.emboj.7600070 . PMC 1271804 PMID 14749727 . Dettwiler S, Aringhieri C, Cardinale S, et al. (2005). "Distinct sequence motifs within the 68-kDa subunit of cleavage factor Im mediate RNA binding, protein-protein interactions, and subcellular localization" (PDF) . J. Biol. Chem . 279 (34): 35788–97. doi :10.1074/jbc.M403927200 PMID 15169763 . Colland F, Jacq X, Trouplin V, et al. (2004). "Functional proteomics mapping of a human signaling pathway" . Genome Res . 14 (7): 1324–32. doi :10.1101/gr.2334104 . PMC 442148 PMID 15231748 . Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins" . Proc. Natl. Acad. Sci. U.S.A . 101 (33): 12130–5. Bibcode :2004PNAS..10112130B . doi :10.1073/pnas.0404720101 PMC 514446 PMID 15302935 . Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)" . Genome Res . 14 (10B): 2121–7. doi :10.1101/gr.2596504 . PMC 528928 PMID 15489334 . Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature . 437 (7062): 1173–8. Bibcode :2005Natur.437.1173R . doi :10.1038/nature04209 . PMID 16189514 . S2CID 4427026 .
PDB gallery
1f5a : CRYSTAL STRUCTURE OF MAMMALIAN POLY(A) POLYMERASE
1q78 : Crystal structure of poly(A) polymerase in complex with 3'-dATP and magnesium chloride
1q79 : CRYSTAL STRUCTURE OF MAMMALIAN POLY(A) POLYMERASE
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