Mechanism of the initiation of mRNA decay: role of eRF3 family G proteins

Abstract

mRNA decay is intimately linked to and regulated by translation in eukaryotes. However, it has remained unclear exactly how mRNA decay is linked to translation. Progress has been made in recent years in understanding the molecular mechanisms of the link between translation and mRNA decay. It has become clear that the eRF3 family of GTP-binding proteins acts as signal transducers that couple translation to mRNA decay and plays pivotal roles in the regulation of gene expression and mRNA quality control. During translation, the translation termination factor eRF3 in complex with eRF1 recognizes the termination codon which appears at the A site of the terminating ribosome. Depending on whether the termination codon is normal (bona fide) or aberrant (premature), deadenylation-dependent decay or nonsense-mediated mRNA decay (NMD) occurs. mRNA without termination codons and mRNA with the propensity to cause the ribosome to stall are recognized as aberrant by other members of the eRF3 family during translation, and these translational events cause nonstop mRNA decay (NSD) and no-go decay (NGD), respectively. In this review, we focus on how mRNA decay is triggered by translational events and summarize the initiation mechanism for the decay of both normal and aberrant mRNAs.