PABPN1 explained

Polyadenylate-binding protein 2 (PABP-2) also known as polyadenylate-binding nuclear protein 1 (PABPN1) is a protein that in humans is encoded by the PABPN1 gene.^{[1] [2]} PABN1 is a member of a larger family of poly(A)-binding proteins in the human genome.

Function

This gene encodes an abundant nuclear protein that binds with high affinity to nascent poly(A) tails. The protein is required for progressive and efficient polymerization of poly(A) tails on the 3' ends of eukaryotic genes and controls the size of the poly(A) tail to about 250 nt. At steady-state, this protein is localized in the nucleus whereas a different poly(A) binding protein is localized in the cytoplasm. An expansion of the trinucleotide (GCN) repeat from normal 10 to 11-17 at the 5' end of the coding region of this gene leads to autosomal dominant oculopharyngeal muscular dystrophy (OPMD) disease.^[3] Multiple splice variants have been described but their full-length nature is not known. One splice variant includes introns 1 and 6 but no protein is formed.^[2]

Interactions

PABPN1 has been shown to interact with SNW1.^[4]

Further reading

• Brais B, Bouchard JP, Xie YG, Rochefort DL, Chrétien N, Tomé FM, Lafrenière RG, Rommens JM, Uyama E, Nohira O, Blumen S, Korczyn AD, Heutink P, Mathieu J, Duranceau A, Codère F, Fardeau M, Rouleau GA, Korcyn AD . Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy . Nat. Genet. . 18 . 2 . 164–7 . 1998 . 9462747 . 10.1038/ng0298-164 . 20485694 .
• Chen Z, Li Y, Krug RM . Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3'-end processing machinery . EMBO J. . 18 . 8 . 2273–83 . 1999 . 10205180 . 1171310 . 10.1093/emboj/18.8.2273 .
• Smith JJ, Rücknagel KP, Schierhorn A, Tang J, Nemeth A, Linder M, Herschman HR, Wahle E . Unusual sites of arginine methylation in Poly(A)-binding protein II and in vitro methylation by protein arginine methyltransferases PRMT1 and PRMT3 . J. Biol. Chem. . 274 . 19 . 13229–34 . 1999 . 10224081 . 10.1074/jbc.274.19.13229 . free .
• Hoshino S, Imai M, Kobayashi T, Uchida N, Katada T . The eukaryotic polypeptide chain releasing factor (eRF3/GSPT) carrying the translation termination signal to the 3'-Poly(A) tail of mRNA. Direct association of erf3/GSPT with polyadenylate-binding protein . J. Biol. Chem. . 274 . 24 . 16677–80 . 1999 . 10358005 . 10.1074/jbc.274.24.16677 . free .
• Féral C, Mattéi MG, Pawlak A, Guellaën G . Chromosomal localization of three human poly(A)-binding protein genes and four related pseudogenes . Hum. Genet. . 105 . 4 . 347–53 . 1999 . 10543404 . 1865476 . 10.1007/s004399900148 .
• Calado A, Kutay U, Kühn U, Wahle E, Carmo-Fonseca M . Deciphering the cellular pathway for transport of poly(A)-binding protein II . RNA . 6 . 2 . 245–56 . 2000 . 10688363 . 1369910 . 10.1017/S1355838200991908 .
• Calado A, Tomé FM, Brais B, Rouleau GA, Kühn U, Wahle E, Carmo-Fonseca M . Nuclear inclusions in oculopharyngeal muscular dystrophy consist of poly(A) binding protein 2 aggregates which sequester poly(A) RNA . Hum. Mol. Genet. . 9 . 15 . 2321–8 . 2001 . 11001936 . 10.1093/oxfordjournals.hmg.a018924 . free .
• Kim YJ, Noguchi S, Hayashi YK, Tsukahara T, Shimizu T, Arahata K . The product of an oculopharyngeal muscular dystrophy gene, poly(A)-binding protein 2, interacts with SKIP and stimulates muscle-specific gene expression . Hum. Mol. Genet. . 10 . 11 . 1129–39 . 2001 . 11371506 . 10.1093/hmg/10.11.1129 . free .
• Fan X, Dion P, Laganiere J, Brais B, Rouleau GA . Oligomerization of polyalanine expanded PABPN1 facilitates nuclear protein aggregation that is associated with cell death . Hum. Mol. Genet. . 10 . 21 . 2341–51 . 2002 . 11689481 . 10.1093/hmg/10.21.2341 . free .
• van der Sluijs BM, van Engelen BG, Hoefsloot LH . Oculopharyngeal muscular dystrophy (OPMD) due to a small duplication in the PABPN1 gene . Hum. Mutat. . 21 . 5 . 553 . 2003 . 12673802 . 10.1002/humu.9138 . 21834985 .
• Fan X, Messaed C, Dion P, Laganiere J, Brais B, Karpati G, Rouleau GA . HnRNP A1 and A/B interaction with PABPN1 in oculopharyngeal muscular dystrophy . The Canadian Journal of Neurological Sciences . 30 . 3 . 244–51 . 2003 . 12945950 . 10.1017/s0317167100002675. free .
• Sugaya K, Matsubara S, Miyamoto K, Kawata A, Hayashi H . An aggregate-prone conformational epitope in trinucleotide repeat diseases . NeuroReport . 14 . 18 . 2331–5 . 2004 . 14663186 . 10.1097/00001756-200312190-00009. 33121469 .
• Villacé P, Marión RM, Ortín J . The composition of Staufen-containing RNA granules from human cells indicates their role in the regulated transport and translation of messenger RNAs . Nucleic Acids Res. . 32 . 8 . 2411–20 . 2004 . 15121898 . 419443 . 10.1093/nar/gkh552 .
• Dettwiler S, Aringhieri C, Cardinale S, Keller W, Barabino SM . 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 .
• Rodríguez M, Camejo C, Bertoni B, Braida C, Rodríguez MM, Brais B, Medici M, Roche L . (GCG)11 founder mutation in the PABPN1 gene of OPMD Uruguayan families . Neuromuscul. Disord. . 15 . 2 . 185–90 . 2005 . 15694141 . 10.1016/j.nmd.2004.10.012 . 34476481 .
• Goh KJ, Wong KT, Nishino I, Minami N, Nonaka I . Oculopharyngeal muscular dystrophy with PABPN1 mutation in a Chinese Malaysian woman . Neuromuscul. Disord. . 15 . 3 . 262–4 . 2005 . 15725589 . 10.1016/j.nmd.2004.10.016 . 20351112 .
• Dion P, Shanmugam V, Gaspar C, Messaed C, Meijer I, Toulouse A, Laganiere J, Roussel J, Rochefort D, Laganiere S, Allen C, Karpati G, Bouchard JP, Brais B, Rouleau GA . Transgenic expression of an expanded (GCG)13 repeat PABPN1 leads to weakness and coordination defects in mice . Neurobiol. Dis. . 18 . 3 . 528–36 . 2005 . 15755680 . 10.1016/j.nbd.2004.09.021 . 39329667 .

External links

• GeneReviews/NCBI/NIH/UW entry on Oculopharyngeal Muscular Dystrophy
• PDBe-KB provides an overview of all the structure information available in the PDB for Human Polyadenylate-binding protein 2

Notes and References

1. Brais B, Xie YG, Sanson M, Morgan K, Weissenbach J, Korczyn AD, Blumen SC, Fardeau M, Tomé FM, Bouchard JP . The oculopharyngeal muscular dystrophy locus maps to the region of the cardiac alpha and beta myosin heavy chain genes on chromosome 14q11.2-q13 . Hum Mol Genet . 4 . 3 . 429–34 . Aug 1995 . 7795598 . 10.1093/hmg/4.3.429 .
2. Web site: Entrez Gene: PABPN1 poly(A) binding protein, nuclear 1.
3. Brais B . Oculopharyngeal muscular dystrophy: a polyalanine myopathy. . Current Neurology and Neuroscience Reports . 9 . 1 . 76–82 . January 2009 . 19080757 . 10.1007/s11910-009-0012-y . 7248907 .
4. Kim YJ, Noguchi S, Hayashi YK, Tsukahara T, Shimizu T, Arahata K . The product of an oculopharyngeal muscular dystrophy gene, poly(A)-binding protein 2, interacts with SKIP and stimulates muscle-specific gene expression . Hum. Mol. Genet. . 10 . 11 . 1129–39 . May 2001 . 11371506 . 10.1093/hmg/10.11.1129 . England . 0964-6906 . free .