翻译延伸的顺式调控机理与生物学效应  

Cis-regulatory mechanisms and biological effects of translation elongation

作　　者：肇涛澜[1] 张硕[1,2] 钱文峰 Taolan Zhao;Shuo Zhang;Wenfeng Qian(State Key Laboratory of Plant Genomics,Institute of Genetics and Developmental Biology,Innovation Academy for Seed Design,Chinese Academy of Sciences,Beijing 100101,China;University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]中国科学院种子创新研究院,中国科学院遗传与发育生物学研究所,植物基因组学国家重点实验室,北京100101 [2]中国科学院大学,北京100049

出　　处：《遗传》2020年第7期613-631,共19页Hereditas（Beijing)

基　　金：国家重点研发计划项目(编号:2019YFA0508700);国家自然科学基金项目(编号:31900455,91331112)资助。

摘　　要：翻译延伸是核糖体将信使RNA(mRNA)蕴含的遗传信息解码为蛋白质的有序过程,是细胞维持基本代谢活动的核心步骤。多种人类疾病(如神经退行性疾病、癌症等)都与翻译延伸的异常有关。翻译延伸作为中心法则的关键步骤曾是现代分子生物学研究的重点内容,然而方法学上的限制却阻碍了对其动态过程以及调控规律的进一步研究。近年来,对翻译延伸调控相关方法的突破让与其相关的生命科学研究获得了长足的发展,尤其是近10年来的研究揭示了翻译延伸的复杂调控机理和多种生物学效应,为理解蛋白表达调控和疾病发生的关联提供了新的理论视角。本文在总结翻译延伸研究方法的基础上,重点探讨了顺式调控元件(mRNA与新生肽链序列)对局部翻译延伸速率的调控作用,同时列举了翻译延伸调控对模板mRNA和蛋白质产物功能的影响,包括mRNA稳定性、蛋白质的合成与降解、蛋白质亚细胞定位以及蛋白质共翻译折叠等,以期吸引生命科学各领域的学者共同参与翻译延伸领域的研究。Proteins are biological macromolecules essential for cells to maintain their metabolic activities.Proteins are synthesized during translation elongation,a synergistic process in which ribosomes decode the genetic information transmitted in mRNA,using tRNA.Numerous human diseases,such as neurodegenerative diseases and cancers,are known to be related to abnormal translation elongation.Translation elongation,as one of the two critical steps for the central dogma,used to be the focus of research in molecular biology.However,limitations in methodology had hindered further investigations on the dynamic process of translation elongation and its regulation.Recently,breakthroughs in methodology have revived this research field.Studies in the past decade or so have revealed that,beyond simple decoding of genetic information in mRNA,translation elongation entails sophisticated regulatory mechanisms and multifaceted biological consequences;such insights have provided a novel theoretical framework for understanding the maintenance of protein homeostasis and the development of diseases.In this review,we summarize the most updated methods that can be used to investigate the processes of translation elongation and highlight the mechanisms by which mRNA and protein sequences modulate the local rate of translation elongation.We further enumerate the consequences of dysregulation in translation elongation,from various aspects such as mRNA stability,protein synthesis and degradation,protein subcellular localization,and co-translational protein folding.We anticipate that this review will serve to draw the attention of scholars in various research fields to participate in the study of translation elongation.

关 键 词：翻译延伸 核糖体 核糖体印迹测序 蛋白质共翻译折叠 密码子使用偏好 RNA二级结构 新生肽链 

分 类 号：Q753[生物学—分子生物学]