Chapter 277 - Regulation of mRNA Turnover

Abstract

This chapter discusses how mRNA decay can be triggered and highlights some recent studies on regulation of mRNA turnover in mammalian cells. mRNA turnover is a complex set of cellular processes regulated by mechanisms independent from transcription. Regulation of mRNA turnover is important for controlling the abundance of cellular transcripts and thus the levels of protein expression. mRNA degradation in the cytoplasm can be initiated by deadenylation, decapping, or endonucleolytic cleavage within the message to generate 5′ and 3′ fragments. mRNA decay pathways in eukaryotic cells involve multiple steps and are more complicated than simply creating free ends by the three theoretical ways followed by exonucleolytic digestion. The importance of deadenylation in regulation of gene expression is further emphasized by two recent developments. First, a group of abundant, evolutionarily conserved small silencing RNAs, termed microRNAs (miRNAs), are capable of promoting decay of their mRNA targets by accelerating deadenylation, thereby achieving gene silencing. Second, non-translatable mRNA-protein complexes (mRNPs) are found in RNA processing bodies, a newly discovered cytoplasmic domain related to translation repression and mRNA decay. Both translation and stability of mRNAs are affected by deadenylation. The importance of deadenylation in mRNA turnover can be observed in all major mRNA decay pathways, including decay directed by AU-rich elements (AREs) in the 3′ UTR, the rapid decay mediated by destabilizing elements in protein coding regions, the surveillance mechanism that detects and degrades nonsense containing mRNA, and the default decay pathway for stable messages such as β-globin mRNA.