Alternative polyadenylation of mRNA precursors

Abstract

Alternative polyadenylation (APA) is an RNA-processing mechanism that generates distinct 3′ termini on mRNAs and other RNA polymerase II transcripts. It is widespread across all eukaryotic species and is recognized as a major mechanism of gene regulation. APA exhibits tissue specificity and is important for cell proliferation and differentiation. In this Review, we discuss the roles of APA in diverse cellular processes, including mRNA metabolism, protein diversification and protein localization, and more generally in gene regulation. We also discuss the molecular mechanisms underlying APA, such as variation in the concentration of core processing factors and RNA-binding proteins, as well as transcription-based regulation.

An Mtr4/ZFC3H1 complex facilitates turnover of unstable nuclear RNAs to prevent their cytoplasmic transport and global translational repression

“…Notably, PROMPTs that are transcribed in the antisense direction, which we specifically refer to as upstream antisense RNAs (uaRNAs) (Flynn et al 2011), appear to be processed by mechanisms of pre-mRNA 3 ′ end formation that are the same as or similar to those of mRNAs (Almada et al 2013;Ntini et al 2013; for review, see . Motifs similar to those that constitute poly(A) sites (PASs) in pre-mRNAs are found at the 3 ′ ends of uaRNAs, and much of the same complex protein machinery that is responsible for mRNA polyadenylation (Tian and Manley 2017) functions in uaRNA 3 ′ end formation . Notably, PASs are more enriched in the upstream antisense region compared with the downstream region, whereas U1 snRNA-binding sites (which, when bound by U1 snRNP, prevent polyadenylation at nearby PASs) (Almada et al 2013;Ntini et al 2013) are more frequent in the sense-coding direction.…”

3′ UTR lengthening as a novel mechanism in regulating cellular senescence

“…Therefore, understanding the regulation of gene expression and the corresponding regulatory networks is crucial to dissecting the mechanism of cellular senescence. Alternative polyadenylation (APA) is recognized as a crucial contributor to the regulation of mammalian gene expression (Di Giammartino et al 2011;Elkon et al 2013;Chen et al 2017;Tian and Manley 2017). Cleavage and polyadenylation of nascent RNA is essential for maturation of the vast majority of eukaryotic mRNAs and determines the length of 3 ′ UTRs (Sachs 1990).…”

“…Alternative pA sites can reside in the 3 ′ -most exon or upstream regions and can give rise to multiple mRNA transcripts that contain different coding sequences, 3 ′ UTRs, or both (Di Giammartino et al 2011;Elkon et al 2013). Importantly, both microRNAs (miRNAs) and RNA binding proteins (RBPs) targeting 3 ′ UTRs are able to regulate translational efficiency, degradation, and subcellular localization of mRNA or protein (Di Giammartino et al 2011;Berkovits and Mayr 2015;Tian and Manley 2017). It is well known that APA plays important roles in a wide range of biological processes such as cell differentiation (Ji et al 2009;Mangone et al 2010;Hilgers et al 2011;Ulitsky et al 2012;Fu et al 2016;Hu et al 2017), cell proliferation Elkon et al 2012;Hoffman et al 2016), cell/tissue identity Derti et al 2012;Smibert et al 2012;Ni et al 2013), and carcinogenesis (Mayr and Bartel 2009;Fu et al 2011;Lin et al 2012;Xia et al 2014).…”

Models of RNA Interaction from Experimental Datasets: Framework of Resilience

“…At various levels, RNA is processed by alternate mechanisms [1], suggesting a biological framework that supports important system network features such as resilience. Trafficking of RNAs is essential for cellular function and homeostasis, but only recently it has become possible to visualize molecular events in vivo.…”