Chapter 270 - Regulation of mRNA Turnover by Cellular Stress

Abstract

This chapter reviews the process of regulated mRNA turnover, one of the most influential mechanisms effecting changes in the patterns of expressed mRNAs in response to stress. By changing the half-lives of mRNAs, which typically range from 20 min to 24 h, mammalian cells can quickly allow certain subsets of mRNAs to accumulate (mRNA stabilization) and rapidly eliminate other subsets of mRNAs (mRNA decay). Among the genes whose expression is regulated through altered mRNA turnover are many encoding T cell activation molecules, cell cycle regulators, cell survival proteins, and stress response factors. The process of mRNA turnover involves the association of trans acting factors that recognize specific cis elements (RNA sequences) on the target mRNA. Two main sets of trans binding factors have been identified: RNA binding proteins (RBPs) and microRNAs. RNP complexes responsible for controlling mRNA stability following stress are regulated by many of the signaling pathways. The plausible mechanisms whereby associations of RNA-binding proteins with turnover-determining sequences can affect mRNA turnover are: RNA-binding proteins may mask/unmask sites of endonucleolytic cleavage; they may enhance or reduce the activity of potential decapping nucleases; they may elevate or diminish the protective influence of PABPs; and they may direct mRNAs to or away from sites in the cell where degradation machineries are at work.