Neeraja , K. Mohanan and Feba, Shaji and Ganesh R, Koshre and Rakesh S., Laishram (2021) Alternative polyadenylation: An enigma of transcript length variation in health and disease. WIREs RNA, 13 (1). ISSN 1757-7012

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Abstract

An overview depicting the role of alternative polyadenylation in disease pathogenesis. Almost all eukaryotic messenger RNAs (mRNAs) undergo polyadenylation at the 3′-end in two concerted steps—endonucleolytic cleavage followed by addition of a poly(A) tail (PA-tail) in the nucleus (Colgan & Manley, 1997; Neve et al., 2017; Shi & Manley, 2015). Polyadenylation is carried out by poly(A) polymerases (PAPs) in a cleavage and polyadenylation (CPA) complex comprised of subunits of CPA specificity factor (CPSF), Cleavage stimulatory factor (CSTF), cleavage factor (CFIm) and (CFIIm), Poly(A) binding protein (PABPN1), and Symplekin as core components (Mandel et al., 2008; J. Zhao et al., 1999). The basic mechanism of 3′-end processing involves recognition of a PA-signal by CPSF subunits, assembly of a CPA complex, endonucleoytic cleavage, and subsequent PA (Neve et al., 2017). List of core CPA factors and their role in the 3′-end processing reaction is detailed in Table 1. Interestingly, over 70% of human genes have multiple polyadenylation sites (PA-sites) at the 3′-UTR that are alternately used for polyadenylation (Derti et al., 2012; Hoque et al., 2013; B. Tian et al., 2005). This alternate usage of PA-sites (known as alternative polyadenylation, APA) generates more than one mRNA isoform with different lengths. The choice of a PA-site is an important determinant of transcript length that can affect both mRNA and protein diversification (Ren et al., 2020; B. Tian & Manley, 2013; Y. Zhang et al., 2021).

Item Type:	Article
Subjects:	Cardiovascular Diseases And Diabetes Biology
Depositing User:	Central Library RGCB
Date Deposited:	21 Feb 2022 09:16
Last Modified:	21 Feb 2022 09:16
URI:	http://rgcb.sciencecentral.in/id/eprint/1123

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