Department of Biochemistry, McGill University, Rosalind and Morris Goodman Cancer Centre, Montreal, Quebec, Canada.
Wiley Interdiscip Rev RNA. 2019 Sep;10(5):e1540. doi: 10.1002/wrna.1540. Epub 2019 May 2.
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.
细胞应激反应是所有生物生存所必需的一种普遍机制。这个多方面的过程主要是通过调节基因表达来产生适合促进细胞存活和恢复的细胞内环境。转录后调控事件被认为是调节 mRNA 转录本核心特征的关键机制,以促进细胞适应各种攻击。虽然诸如 mRNA 剪接、周转、定位和翻译等过程对细胞应激反应的影响已经得到了广泛的研究,但最近的观察结果强调了可变多聚腺苷酸化 (APA) 在应对氧化应激、热休克和饥饿等挑战中的作用。APA 的作用是全面的,对 mRNA 稳定性、mRNA 定位和蛋白质编码序列都有深远的影响。尽管 APA 在调节应激反应的关键介质中发挥着重要作用,但它仍然是一种相对未被充分认识的基因调控方式。这篇综述的目的是概述我们对 APA 通过多种方式影响细胞适应其环境的理解的最新进展,并讨论 APA 的缺陷如何对细胞存活产生有害影响。本文属于以下分类:RNA 在疾病与发育中的作用 > RNA 在疾病中的作用 RNA 结构与动态 > RNA 结构对生物系统的影响 RNA 加工 > 3' 端加工。