Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
Wiley Interdiscip Rev RNA. 2012 Nov-Dec;3(6):743-57. doi: 10.1002/wrna.1133. Epub 2012 Sep 10.
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.
mRNA 的降解与真核生物中的翻译密切相关并受其调控。然而，mRNA 的降解与翻译的确切联系仍不清楚。近年来，人们在理解翻译与 mRNA 降解之间联系的分子机制方面取得了进展。很明显，eRF3 家族的 GTP 结合蛋白作为信号转导因子，将翻译与 mRNA 降解偶联起来，并在基因表达和 mRNA 质量控制的调节中发挥关键作用。在翻译过程中，翻译终止因子 eRF3 与 eRF1 复合物识别出出现在终止核糖体 A 位的终止密码子。根据终止密码子是否正常（真实）或异常（提前），发生依赖于脱腺苷酸化的降解或无意义介导的 mRNA 降解（NMD）。在翻译过程中，其他 eRF3 家族成员将没有终止密码子的 mRNA 和有导致核糖体停滞倾向的 mRNA 识别为异常，这些翻译事件分别导致非终止 mRNA 降解（NSD）和无终止降解（NGD）。在这篇综述中，我们重点讨论了翻译事件如何触发 mRNA 的降解，并总结了正常和异常 mRNA 降解的起始机制。
