Manjunath Lekha E, Singh Anumeha, Som Saubhik, Eswarappa Sandeep M
Department of Biochemistry, Indian Institute of Science, Bengaluru, Karnataka, India.
Wiley Interdiscip Rev RNA. 2023 Mar;14(2):e1739. doi: 10.1002/wrna.1739. Epub 2022 May 15.
Recognition of a stop codon by translation machinery as a sense codon results in translational readthrough instead of termination. This recoding process, termed stop codon readthrough (SCR) or translational readthrough, is found in all domains of life including mammals. The context of the stop codon, local mRNA topology, and molecules that interact with the mRNA region downstream of the stop codon determine SCR. The products of SCR can have localization, stability, and function different from those of the canonical isoforms. In this review, we discuss how recent technological and computational advances have increased our understanding of the SCR process in the mammalian system. Based on the known molecular events that occur during SCR of multiple mRNAs, we propose transient molecular roadblocks on an mRNA downstream of the stop codon as a possible mechanism for the induction of SCR. We argue, with examples, that the insights gained from the natural SCR events can guide us to develop novel strategies for the treatment of diseases caused by premature stop codons. This article is categorized under: Translation > Regulation.
翻译机制将终止密码子识别为有义密码子会导致翻译通读而非终止。这种重新编码过程，称为终止密码子通读（SCR）或翻译通读，在包括哺乳动物在内的所有生命领域中都存在。终止密码子的上下文、局部mRNA拓扑结构以及与终止密码子下游mRNA区域相互作用的分子决定了SCR。SCR的产物可能具有与经典异构体不同的定位、稳定性和功能。在本综述中，我们讨论了最近的技术和计算进展如何增进了我们对哺乳动物系统中SCR过程的理解。基于多个mRNA的SCR过程中发生的已知分子事件，我们提出终止密码子下游mRNA上的瞬时分子障碍是诱导SCR的一种可能机制。我们举例说明，从自然SCR事件中获得的见解可以指导我们开发治疗由提前终止密码子引起的疾病的新策略。本文分类如下：翻译>调控。
