Fates and functions of RNA-binding proteins under stress.

IF 6.4 2区 生物学 Q1 CELL BIOLOGY
Binita Goswami, Sharanya Nag, Partho Sarothi Ray
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Abstract

Exposure to stress activates a well-orchestrated set of changes in gene expression programs that allow the cell to cope with and adapt to the stress, or undergo programmed cell death. RNA-protein interactions, mediating all aspects of post-transcriptional regulation of gene expression, play crucial roles in cellular stress responses. RNA-binding proteins (RBPs), which interact with sequence/structural elements in RNAs to control the steps of RNA metabolism, have therefore emerged as central regulators of post-transcriptional responses to stress. Following exposure to a variety of stresses, the dynamic alterations in the RNA-protein interactome enable cells to respond to intracellular or extracellular perturbations by causing changes in mRNA splicing, polyadenylation, stability, translation, and localization. As RBPs play a central role in determining the cellular proteome both qualitatively and quantitatively, it has become increasingly evident that their abundance, availability, and functions are also highly regulated in response to stress. Exposure to stress initiates a series of signaling cascades that converge on post-translational modifications (PTMs) of RBPs, resulting in changes in their subcellular localization, association with stress granules, extracellular export, proteasomal degradation, and RNA-binding activities. These alterations in the fate and function of RBPs directly impact their post-transcriptional regulatory roles in cells under stress. Adopting the ubiquitous RBP HuR as a prototype, three scenarios illustrating the changes in nuclear-cytoplasmic localization, RNA-binding activity, export and degradation of HuR in response to inflammation, genotoxic stress, and heat shock depict the complex and interlinked regulatory mechanisms that control the fate and functions of RBPs under stress. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.

Abstract Image

应激条件下rna结合蛋白的命运和功能。
暴露在压力下会激活基因表达程序中一系列精心安排的变化,这些变化允许细胞应对和适应压力,或者经历程序性细胞死亡。rna -蛋白相互作用介导了基因表达转录后调控的各个方面,在细胞应激反应中起着至关重要的作用。RNA结合蛋白(rbp)与RNA中的序列/结构元件相互作用以控制RNA代谢的步骤,因此成为应激后转录反应的中心调节因子。在暴露于各种压力后,rna -蛋白相互作用组的动态变化使细胞能够通过引起mRNA剪接、聚腺苷化、稳定性、翻译和定位的变化来响应细胞内或细胞外的扰动。由于rbp在定性和定量上决定细胞蛋白质组的核心作用,越来越明显的是,它们的丰度、可用性和功能在应激反应中也受到高度调节。应激触发一系列信号级联反应,这些信号级联反应集中在rbp的翻译后修饰(PTMs)上,导致其亚细胞定位、与应激颗粒、细胞外输出、蛋白酶体降解和rna结合活性的关联发生变化。rbp的命运和功能的这些改变直接影响它们在应激细胞中的转录后调节作用。以普遍存在的RBP HuR为原型,在炎症反应、基因毒性应激和热休克的情况下,核胞质定位、rna结合活性、HuR的输出和降解发生了三种变化,描述了应激下控制RBP命运和功能的复杂而相互关联的调节机制。本文分类如下:RNA与蛋白质和其他分子的相互作用>蛋白质-RNA相互作用:功能意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
14.80
自引率
4.10%
发文量
67
审稿时长
6-12 weeks
期刊介绍: WIREs RNA aims to provide comprehensive, up-to-date, and coherent coverage of this interesting and growing field, providing a framework for both RNA experts and interdisciplinary researchers to not only gain perspective in areas of RNA biology, but to generate new insights and applications as well. Major topics to be covered are: RNA Structure and Dynamics; RNA Evolution and Genomics; RNA-Based Catalysis; RNA Interactions with Proteins and Other Molecules; Translation; RNA Processing; RNA Export/Localization; RNA Turnover and Surveillance; Regulatory RNAs/RNAi/Riboswitches; RNA in Disease and Development; and RNA Methods.
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