遗传 ›› 2020, Vol. 42 ›› Issue (7): 613-631.doi: 10.16288/j.yczz.20-074

• 特邀综述 •    下一篇

翻译延伸的顺式调控机理与生物学效应

肇涛澜1, 张硕1,2, 钱文峰1,2()   

  1. 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
  • 收稿日期:2020-03-18 修回日期:2020-06-28 出版日期:2020-07-20 发布日期:2020-07-07
  • 通讯作者: 钱文峰 E-mail:wfqian@genetics.ac.cn
  • 作者简介:肇涛澜,博士,研究方向:翻译调控。E-mail: tlzhao@genetics.ac.cn|张硕,在读硕士研究生,专业方向:翻译调控。E-mail: shzhang@genetics.ac.cn; 肇涛澜和张硕为并列第一作者|钱文峰课题组的主要研究方向之一是蛋白质翻译调控及其进化。建立在高通量的报告基因突变体蛋白质水平测定(sort-seq)和翻译组学(ribo-seq)两大技术的基础上,以酿酒酵母、拟南芥、线虫等多个具有进化代表意义的物种为研究材料,系统鉴定了参与翻译调控的顺式作用元件和反式作用因子,并探究了它们的细胞生物学效应。发现了反式剪接和poly(A)尾中的鸟嘌呤可以调控蛋白质翻译效率,同义密码子可以通过翻译延伸速率调控mRNA稳定性,以及蛋白质质量控制机制参与调控非整倍体细胞蛋白质的剂量平衡。相关研究成果发表在Genome Biology、Genome Research、Cell Systems、Molecular Biology and Evolution等期刊上。现主持国家重点研发计划“蛋白质机器与生命过程调控”青年项目1项。
  • 基金资助:
    国家重点研发计划项目编号(2019YFA0508700);国家自然科学基金项目资助编号(31900455);国家自然科学基金项目资助编号(91331112)

Cis-regulatory mechanisms and biological effects of translation elongation

Zhao Taolan1, Zhang Shuo1,2, Qian Wenfeng1,2()   

  1. 1. State Key Laboratory of Plant Genomics, Institute of Genetics and Developmental Biology, Innovation Academy for Seed Design, Chinese Academy of Sciences, Beijing 100101, China
    2. University of Chinese Academy of Sciences, Beijing 100049, China
  • Received:2020-03-18 Revised:2020-06-28 Online:2020-07-20 Published:2020-07-07
  • Contact: Qian Wenfeng E-mail:wfqian@genetics.ac.cn
  • Supported by:
    Supported by the National Key R&D Program of China No(2019YFA0508700);the National Natural Science Foundation of China Nos(31900455);the National Natural Science Foundation of China Nos(91331112)

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。

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

Abstract:

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.

Key words: translation elongation, ribosome, ribo-seq, co-translational protein folding, codon usage bias, RNA secondary structure, nascent polypeptide