Zhao Qi, Pavanello Lorenzo, Bartlam Mark, Winkler Gerlof Sebastiaan
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai International Advanced Research Institute (Shenzhen Futian), Nankai University, Tianjin, China.
School of Pharmacy, University of Nottingham, University Park, Nottingham, United Kingdom.
Front Genet. 2023 Oct 9;14:1233842. doi: 10.3389/fgene.2023.1233842. eCollection 2023.
In eukaryotic cells, the synthesis, processing, and degradation of mRNA are important processes required for the accurate execution of gene expression programmes. Fully processed cytoplasmic mRNA is characterised by the presence of a 5'cap structure and 3'poly(A) tail. These elements promote translation and prevent non-specific degradation. Degradation via the deadenylation-dependent 5'-3' degradation pathway can be induced by trans-acting factors binding the mRNA, such as RNA-binding proteins recognising sequence elements and the miRNA-induced repression complex. These factors recruit the core mRNA degradation machinery that carries out the following steps: i) shortening of the poly(A) tail by the Ccr4-Not and Pan2-Pan3 poly (A)-specific nucleases (deadenylases); ii) removal of the 5'cap structure by the Dcp1-Dcp2 decapping complex that is recruited by the Lsm1-7-Pat1 complex; and iii) degradation of the mRNA body by the 5'-3' exoribonuclease Xrn1. In this review, the biochemical function of the nucleases and accessory proteins involved in deadenylation-dependent mRNA degradation will be reviewed with a particular focus on structural aspects of the proteins and enzymes involved.
在真核细胞中，mRNA的合成、加工和降解是准确执行基因表达程序所需的重要过程。完全加工后的细胞质mRNA的特征是存在5'帽结构和3'多聚腺苷酸尾。这些元件促进翻译并防止非特异性降解。通过依赖于去腺苷酸化的5'-3'降解途径进行的降解可由与mRNA结合的反式作用因子诱导，例如识别序列元件的RNA结合蛋白和miRNA诱导的抑制复合物。这些因子招募核心mRNA降解机制，该机制执行以下步骤：i）由Ccr4-Not和Pan2-Pan3多聚（A）特异性核酸酶（去腺苷酸酶）缩短多聚（A）尾；ii）由Lsm1-7-Pat1复合物招募的Dcp1-Dcp2脱帽复合物去除5'帽结构；iii）由5'-3'外切核糖核酸酶Xrn1降解mRNA主体。在本综述中，将对参与依赖去腺苷酸化的mRNA降解的核酸酶和辅助蛋白的生化功能进行综述，特别关注所涉及的蛋白质和酶的结构方面。
