Fates and functions of RNA‐binding proteins under stress

Abstract

AbstractExposure 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