Cytoplasmic mRNA decay and quality control machineries in eukaryotes

Abstract

mRNA degradation pathways have key regulatory roles in gene expression. The intrinsic stability of mRNAs in the cytoplasm of eukaryotic cells varies widely in a gene- and isoform-dependent manner and can be regulated by cellular cues, such as kinase signalling, to control mRNA levels and spatiotemporal dynamics of gene expression. Moreover, specialized quality control pathways exist to rid cells of non-functional mRNAs produced by errors in mRNA processing or mRNA damage that negatively impact translation. Recent advances in structural, single-molecule and genome-wide methods have provided new insights into the central machineries that carry out mRNA turnover, the mechanisms by which mRNAs are targeted for degradation and the general principles that govern mRNA stability at a global level. This improved understanding of mRNA degradation in the cytoplasm of eukaryotic cells is finding practical applications in the design of therapeutic mRNAs. In this Review, Dowdle and Lykke-Andersen discuss advances in our understanding of the machinery and mechanisms involved in the control of cytoplasmic mRNA decay and comment on implications for the design of therapeutic mRNAs.