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Turnover of AU‐rich‐containing mRNAs during stress: a matter of survival

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Abstract Cells undergo various adaptive measures in response to stress. Among these are specific changes in the posttranscriptional regulation of various genes. In particular, the turnover of mRNA is modified to either increase or decrease the abundance of certain target messages. Some of the best‐studied mRNAs that are affected by stress are those that contain adenine/uridine‐rich elements (AREs) in their 3′‐untranslated regions. ARE‐containing mRNAs are involved in many important cellular processes and are normally labile, but in response to stress they are differentially regulated through the concerted efforts of ARE‐binding proteins (AUBPs) such as HuR, AUF1, tristetraprolin, BRF1, and KSRP, along with microRNA‐mediated effects. Additionally, the fate of ARE‐containing mRNAs is modified by inducing their localization to stress granules or mRNA processing bodies. Coordination of these various mechanisms controls the turnover of ARE‐containing mRNAs, and thereby enables proper responses to cellular stress. In this review, we discuss how AUBPs regulate their target mRNAs in response to stress, along with the involvement of cytoplasmic granules in this process. WIREs RNA 2011 2 336–347 DOI: 10.1002/wrna.55 This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms RNA Turnover and Surveillance > Regulation of RNA Stability

The four pillars of cellular stress response. In response to stress stimuli, cells optimize their resources and adapt appropriately. We propose that this response consists of four fundamental activities that are described in detail in the text.

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Triage of adenine/uridine‐rich element (ARE)‐mRNAs in response to stress. In response to stress, ARE‐containing mRNAs have their turnover regulated. mRNAs translocate to specific cytoplasmic foci, either stress granules (SGs) or processing bodies (PBs), and are then thought to be stabilized or decayed, respectively. It is unclear, however, how SGs and PBs interact to mediate these effects, and whether or not they can each individually influence the stabilization or decay of target transcripts (represented by question marks and dashed lines).

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RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications
RNA Turnover and Surveillance > Regulation of RNA Stability
RNA Turnover and Surveillance > Turnover/Surveillance Mechanisms

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