PAPOLA explained

Poly(A) polymerase alpha is an enzyme that in humans is encoded by the PAPOLA gene.^{[1] [2] [3]}

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.^[4]

Further reading

• Weichs an der Glon C, Ashe M, Eggermont J, Proudfoot NJ . Tat-dependent occlusion of the HIV poly(A) site. . EMBO J. . 12 . 5 . 2119–28 . 1993 . 8491200 . 10.1002/j.1460-2075.1993.tb05860.x. 413433 .
• Pendurthi UR, Alok D, Rao LV . 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 . 1997 . 9356495 . 10.1073/pnas.94.23.12598 . 25051 . 1997PNAS...9412598P . free .
• Varani L, Gunderson SI, Mattaj IW, etal . 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 . 2000 . 10742179 . 10.1038/74101 . 13432764 .
• Mouland AJ, Coady M, Yao XJ, Cohen EA . Hypophosphorylation of poly(A) polymerase and increased polyadenylation activity are associated with human immunodeficiency virus type 1 Vpr expression. . Virology . 292 . 2 . 321–30 . 2002 . 11878934 . 10.1006/viro.2001.1261 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . 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 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Kim H, Lee JH, Lee Y . Regulation of poly(A) polymerase by 14-3-3epsilon. . EMBO J. . 22 . 19 . 5208–19 . 2003 . 14517258 . 10.1093/emboj/cdg486 . 204469 .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Bouwmeester T, Bauch A, Ruffner H, etal . A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. . Nat. Cell Biol. . 6 . 2 . 97–105 . 2004 . 14743216 . 10.1038/ncb1086 . 11683986 .
• Kaufmann I, Martin G, Friedlein A, etal . 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 . 2005 . 14749727 . 10.1038/sj.emboj.7600070 . 1271804 .
• Dettwiler S, Aringhieri C, Cardinale S, etal . Distinct sequence motifs within the 68-kDa subunit of cleavage factor Im mediate RNA binding, protein-protein interactions, and subcellular localization. . J. Biol. Chem. . 279 . 34 . 35788–97 . 2005 . 15169763 . 10.1074/jbc.M403927200 . free .
• Colland F, Jacq X, Trouplin V, etal . Functional proteomics mapping of a human signaling pathway. . Genome Res. . 14 . 7 . 1324–32 . 2004 . 15231748 . 10.1101/gr.2334104 . 442148 .
• Beausoleil SA, Jedrychowski M, Schwartz D, etal . Large-scale characterization of HeLa cell nuclear phosphoproteins. . Proc. Natl. Acad. Sci. U.S.A. . 101 . 33 . 12130–5 . 2004 . 15302935 . 10.1073/pnas.0404720101 . 514446 . 2004PNAS..10112130B . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Rual JF, Venkatesan K, Hao T, etal . Towards a proteome-scale map of the human protein-protein interaction network. . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .

Notes and References

1. Thuresson AC, Astrom J, Astrom A, Gronvik KO, Virtanen A . Multiple forms of poly(A) polymerases in human cells . Proc Natl Acad Sci U S A . 91 . 3 . 979–83 . Mar 1994 . 8302877 . 521437 . 10.1073/pnas.91.3.979 . 1994PNAS...91..979T . free .
2. Yamauchi T, Sugimoto J, Hatakeyama T, Asakawa S, Shimizu N, Isobe M . 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 . Sep 1999 . 10429366 . 10.1007/s100380050154 . free .
3. Web site: Entrez Gene: PAPOLA poly(A) polymerase alpha.
4. Web site: FIP1L1 factor interacting with PAPOLA and CPSF1 [Homo sapiens (Human)] - Gene - NCBI.