RNA Therapeutics Institute, Department of Biochemistry and Molecular Pharmacology, UMass Medical School, Worcester, MA, USA.
Biochemistry (Mosc). 2021 Sep;86(9):1107-1121. doi: 10.1134/S0006297921090066.
When a ribosome encounters the stop codon of an mRNA, it terminates translation, releases the newly made protein, and is recycled to initiate translation on a new mRNA. Termination is a highly dynamic process in which release factors (RF1 and RF2 in bacteria; eRF1•eRF3•GTP in eukaryotes) coordinate peptide release with large-scale molecular rearrangements of the ribosome. Ribosomes stalled on aberrant mRNAs are rescued and recycled by diverse bacterial, mitochondrial, or cytoplasmic quality control mechanisms. These are catalyzed by rescue factors with peptidyl-tRNA hydrolase activity (bacterial ArfA•RF2 and ArfB, mitochondrial ICT1 and mtRF-R, and cytoplasmic Vms1), that are distinct from each other and from release factors. Nevertheless, recent structural studies demonstrate a remarkable similarity between translation termination and ribosome rescue mechanisms. This review describes how these pathways rely on inherent ribosome dynamics, emphasizing the active role of the ribosome in all translation steps.
当核糖体遇到 mRNA 的终止密码子时,它会终止翻译,释放新合成的蛋白质,并被回收以在新的 mRNA 上启动翻译。终止是一个高度动态的过程,在此过程中,释放因子(细菌中的 RF1 和 RF2;真核生物中的 eRF1•eRF3•GTP)协调肽的释放与核糖体的大规模分子重排。由各种细菌、线粒体或细胞质质量控制机制挽救和回收在异常 mRNA 上停滞的核糖体。这些机制由具有肽基-tRNA 水解酶活性的挽救因子(细菌中的 ArfA•RF2 和 ArfB、线粒体中的 ICT1 和 mtRF-R 以及细胞质中的 Vms1)催化,它们彼此不同,也与释放因子不同。然而,最近的结构研究表明,翻译终止和核糖体挽救机制之间存在显著的相似性。这篇综述描述了这些途径如何依赖于核糖体固有的动力学,强调了核糖体在所有翻译步骤中的主动作用。