Historical Background
RNA processing is a critical step in gene expression. RNA-binding proteins are involved in every aspect of RNA processing including splicing, polyadenylation, nuclear export, translation, localization, and, eventually, RNA turnover. Polyadenylate-binding nuclear protein 1 (PABPN1) is an RNA-binding protein that is predominantly localized to the nucleus where its canonical function is to regulate polyadenosine [poly(A)] tail addition by first stimulating poly(A) polymerase (PAP) activity and then limiting poly(A) tail length (Wahle 1991, Kuhn et al. 2009). PABPN1 is also involved in RNA export from the nucleus, the pioneer round of translation, and targeting some specific RNAs for decay (Banerjee et al. 2013). Although PABPN1 was originally cloned and characterized as an RNA recognition motif (RRM)-containing RNA-binding protein, interest in the protein greatly increased when mutations that modestly expand an N-terminal alanine...
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References
Anvar SY, Raz Y, Verway N, van der Sluijs B, Venema A, Goeman JJ, et al. A decline in PABPN1 induces progressive muscle weakness in oculopharyngeal muscle dystrophy and in muscle aging. Aging (Albany NY). 2013;5(6):412–26.
Apponi LH, Corbett AH, Pavlath GK. Control of mRNA stability contributes to low levels of nuclear poly(A) binding protein 1 (PABPN1) in skeletal muscle. Skelet Muscle. 2013;3(1):23.
Apponi LH, Leung SW, Williams KR, Valentini SR, Corbett AH, Pavlath GK. Loss of nuclear poly(A)-binding protein 1 causes defects in myogenesis and mRNA biogenesis. Hum Mol Genet. 2010;19(6):1058–65.
Banerjee A, Apponi LH, Pavlath GK, Corbett AH. PABPN1: molecular function and muscle disease. FEBS J. 2013;280(17):4230–50.
Beaulieu YB, Kleinman CL, Landry-Voyer AM, Majewski J, Bachand F. Polyadenylation-dependent control of long noncoding RNA expression by the poly(A)-binding protein nuclear 1. PLoS Genet. 2012;8(11):e1003078.
Bergeron D, Pal G, Beaulieu YB, Chabot B, Bachand F. Regulated intron retention and nuclear pre-mRNA decay contribute to PABPN1 autoregulation. Mol Cell Biol. 2015;35(14):2503–17.
Brais B, Bouchard JP, Xie YG, Rochefort DL, Chretien N, Tome FM, et al. Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy. Nat Genet. 1998;18(2):164–7.
Bresson SM, Conrad NK. The human nuclear poly(a)-binding protein promotes RNA hyperadenylation and decay. PLoS Genet. 2013;9(10):e1003893.
Bresson SM, Hunter OV, Hunter AC, Conrad NK. Canonical poly(A) polymerase activity promotes the decay of a wide variety of mammalian nuclear RNAs. PLoS Genet. 2015;11(10):e1005610.
Creemers EE, Bawazeer A, Ugalde AP, van Deutekom HW, van der Made I, de Groot NE, et al. Genome-wide polyadenylation maps reveal dynamic mRNA 3′-end formation in the failing human heart. Circ Res. 2016;118(3):433–8.
Davies JE, Sarkar S, Rubinsztein DC. Wild-type PABPN1 is anti-apoptotic and reduces toxicity of the oculopharyngeal muscular dystrophy mutation. Hum Mol Genet. 2008;17(8):1097–108.
Davies JE, Wang L, Garcia-Oroz L, Cook LJ, Vacher C, O’Donovan DG, et al. Doxycycline attenuates and delays toxicity of the oculopharyngeal muscular dystrophy mutation in transgenic mice. Nat Med. 2005;11(6):672–7.
de Klerk E, Venema A, Anvar SY, Goeman JJ, Hu O, Trollet C, et al. Poly(A) binding protein nuclear 1 levels affect alternative polyadenylation. Nucleic Acids Res. 2012;40(18):9089–101.
Elkon R, Ugalde AP, Agami R. Alternative cleavage and polyadenylation: extent, regulation and function. Nat Rev Genet. 2013;14(7):496–506.
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. 2001;10(21):2341–51.
Fan X, Messaed C, Dion P, Laganiere J, Brais B, Karpati G, et al. HnRNP A1 and A/B interaction with PABPN1 in oculopharyngeal muscular dystrophy. Can J Neurol Sci. 2003;30(3):244–51.
Ichinose J, Watanabe K, Sano A, Nagase T, Nakajima J, Fukayama M, et al. Alternative polyadenylation is associated with lower expression of PABPN1 and poor prognosis in non-small cell lung cancer. Cancer Sci. 2014;105(9):1135–41.
Ishigaki Y, Li X, Serin G, Maquat LE. Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20. Cell. 2001;106(5):607–17.
Jenal M, Elkon R, Loayza-Puch F, van Haaften G, Kuhn U, Menzies FM, et al. The poly(A)-binding protein nuclear 1 suppresses alternative cleavage and polyadenylation sites. Cell. 2012;149(3):538–53.
Klein P, Oloko M, Roth F, Montel V, Malerba A, Jarmin S, et al. Nuclear poly(A)-binding protein aggregates misplace a pre-mRNA outside of SC35 speckle causing its abnormal splicing. Nucleic Acids Res. 2016; 44:10929–45.
Kuhn U, Gundel M, Knoth A, Kerwitz Y, Rudel S, Wahle E. Poly(A) tail length is controlled by the nuclear poly(A)-binding protein regulating the interaction between poly(A) polymerase and the cleavage and polyadenylation specificity factor. J Biol Chem. 2009;284(34):22803–14.
Kusters B, van Hoeve BJ, Schelhaas HJ, Ter Laak H, van Engelen BG, Lammens M. TDP-43 accumulation is common in myopathies with rimmed vacuoles. Acta Neuropathol. 2009;117(2):209–11.
Lee M, Kwon DY, Kim MS, Choi CR, Park MY, Kim AJ. Genome-wide association study for the interaction between BMR and BMI in obese Korean women including overweight. Nutr Res Pract. 2016;10(1):115–24.
Lemay JF, D’Amours A, Lemieux C, Lackner DH, St-Sauveur VG, Bahler J, et al. The nuclear poly(A)-binding protein interacts with the exosome to promote synthesis of noncoding small nucleolar RNAs. Mol Cell. 2010;37(1):34–45.
Lemieux C, Bachand F. Cotranscriptional recruitment of the nuclear poly(A)-binding protein Pab2 to nascent transcripts and association with translating mRNPs. Nucleic Acids Res. 2009;37(10):3418–30.
Li W, You B, Hoque M, Zheng D, Luo W, Ji Z, et al. Systematic profiling of poly(A)+ transcripts modulated by core 3′ end processing and splicing factors reveals regulatory rules of alternative cleavage and polyadenylation. PLoS Genet. 2015;11(4):e1005166.
Muniz L, Davidson L, West S. Poly(A) polymerase and the nuclear poly(A) binding protein, PABPN1, coordinate the splicing and degradation of a subset of human pre-mRNAs. Mol Cell Biol. 2015;35(13):2218–30.
Ohshima K, Kanto K, Hatakeyama K, Ide T, Wakabayashi-Nakao K, Watanabe Y, et al. Exosome-mediated extracellular release of polyadenylate-binding protein 1 in human metastatic duodenal cancer cells. Proteomics. 2014;14(20):2297–306.
Raz V, Buijze H, Raz Y, Verwey N, Anvar SY, Aartsma-Rus A, et al. A novel feed-forward loop between ARIH2 E3-ligase and PABPN1 regulates aging-associated muscle degeneration. Am J Pathol. 2014;184(4):1119–31.
Riaz M, Raz Y, van Putten M, Paniagua-Soriano G, Krom YD, Florea BI, et al. PABPN1-dependent mRNA processing induces muscle wasting. PLoS Genet. 2016;12(5):e1006031.
Tavanez JP, Calado P, Braga J, Lafarga M, Carmo-Fonseca M. In vivo aggregation properties of the nuclear poly(A)-binding protein PABPN1. RNA. 2005;11(5):752–62.
Wahle E. A novel poly(A)-binding protein acts as a specificity factor in the second phase of messenger RNA polyadenylation. Cell. 1991;66(4):759–68.
Wahle E, Lustig A, Jeno P, Maurer P. Mammalian poly(A)-binding protein II. Physical properties and binding to polynucleotides. J Biol Chem. 1993;268(4):2937–45.
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Phillips, B.L., Corbett, A.H., Vest, K.E. (2018). PABPN1. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101742
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DOI: https://doi.org/10.1007/978-3-319-67199-4_101742
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