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Alternative polyadenylation and the stress response

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Abstract The cellular stress response is a universal mechanism necessary for the survival of all organisms. This multifaceted process is primarily driven by regulation of gene expression to produce an intracellular environment suitable for promoting cell survival and recovery. Posttranscriptional regulatory events are considered as critical mechanisms that modulate core characteristics of mRNA transcripts to promote cell adaptation to various assaults. While the impact of processes such as mRNA splicing, turnover, localization, and translation on the cellular stress response has been extensively studied, recent observations highlight the role of alternative polyadenylation (APA) in response to challenges such as oxidative stress, heat shock, and starvation. The role of APA is comprehensive with far reaching effects on mRNA stability, mRNA localization, and protein coding sequences. Nonetheless, APA remains a relatively unappreciated mode of gene regulation despite its role in regulating key mediators of the stress response. The goal of this review is to provide an overview of the recent advances in our understanding of the various ways by which APA affects cell adaptation to its environment and discuss how a defect in APA could have deleterious consequences on cell survival. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Processing > 3′ End Processing
Schematic of core cis‐elements and trans‐factors involved in polyadenylation. (a) The relative positions of the cis‐elements utilized in polyadenylation are portrayed. (b) The assembly of core factors involved in cleavage and polyadenylation and their characterized binding to each other and cis‐elements is highlighted before the cleavage occurs. (c) The polyadenylation of the cleaved mRNA is depicted. CFIIm, cleavage factors IIm; CFIm, cleavage factors Im; CPSF, cleavage and polyadenylation specificity factor; CstF, cleavage stimulating factor; CTD, carboxyterminal domain; DSE, Downstream element; P, phosphorylated serines; PABPN1, nuclear poly(A) binding protein; PAP, poly(A) polymerase; PAS, poly(A) signal; RNAPII, RNA polymerase II; USE, upstream element; XA, cleavage site
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Schematic of characterized variants of APA. The various outcomes of APA are depicted. In 3′ UTR‐APA, note the addition of regulatory sequences found in the long isoform of the mRNA when distal sites are chosen. APA, alternative polyadenylation
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RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems
RNA Processing > 3′ End Processing
RNA in Disease and Development > RNA in Disease

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