真核生物翻译起始的分子基础及其调控

IF 81.3 1区 生物学 Q1 CELL BIOLOGY
Jailson Brito Querido, Irene Díaz-López, V. Ramakrishnan
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引用次数: 0

摘要

基因表达的调控是生命的基础。虽然转录调控基因表达的作用已经研究了几十年,但在过去的二十年中,人们已经清楚地认识到,基因表达的转录后调控(其中翻译调控是主要部分)也同样重要。翻译可分为起始、延伸、终止和核糖体再循环四个主要阶段。翻译主要在起始过程中受到控制,这一过程在核糖体与起始密码子上方的启动tRNA定位时达到高潮,因此,准备开始蛋白质链的延伸。mRNA翻译已成为开发创新疗法的有力工具,但复杂起始过程背后的详细机制尚不清楚。最近对酵母和哺乳动物的研究已经开始揭示这一过程中一些以前不清楚的方面。本文就真核生物翻译起始及其在健康和疾病中的调控的研究现状进行综述。具体来说,我们关注于了解43S起始前复合物的组装及其在mRNA 5 '端由帽结合复合物真核翻译起始因子4F (eIF4F)募集的过程的最新进展。此外,我们还讨论了最近对核糖体沿着mRNA的5 '非翻译区扫描和起始密码子选择的见解,这些选择最终导致60S大亚基的加入和80S起始复合物的形成。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The molecular basis of translation initiation and its regulation in eukaryotes

The molecular basis of translation initiation and its regulation in eukaryotes

The molecular basis of translation initiation and its regulation in eukaryotes
The regulation of gene expression is fundamental for life. Whereas the role of transcriptional regulation of gene expression has been studied for several decades, it has been clear over the past two decades that post-transcriptional regulation of gene expression, of which translation regulation is a major part, can be equally important. Translation can be divided into four main stages: initiation, elongation, termination and ribosome recycling. Translation is controlled mainly during its initiation, a process which culminates in a ribosome positioned with an initiator tRNA over the start codon and, thus, ready to begin elongation of the protein chain. mRNA translation has emerged as a powerful tool for the development of innovative therapies, yet the detailed mechanisms underlying the complex process of initiation remain unclear. Recent studies in yeast and mammals have started to shed light on some previously unclear aspects of this process. In this Review, we discuss the current state of knowledge on eukaryotic translation initiation and its regulation in health and disease. Specifically, we focus on recent advances in understanding the processes involved in assembling the 43S pre-initiation complex and its recruitment by the cap-binding complex eukaryotic translation initiation factor 4F (eIF4F) at the 5′ end of mRNA. In addition, we discuss recent insights into ribosome scanning along the 5′ untranslated region of mRNA and selection of the start codon, which culminates in joining of the 60S large subunit and formation of the 80S initiation complex. Translation is controlled mainly during its initiation. Recent studies in yeast and mammals provide new insights into the mechanism of translation initiation regulation in health and in various diseases, and open avenues for the development of innovative therapies targeting the translation machinery.
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来源期刊
Nature Reviews Molecular Cell Biology
Nature Reviews Molecular Cell Biology 生物-细胞生物学
CiteScore
173.60
自引率
0.50%
发文量
118
审稿时长
6-12 weeks
期刊介绍: Nature Reviews Molecular Cell Biology is a prestigious journal that aims to be the primary source of reviews and commentaries for the scientific communities it serves. The journal strives to publish articles that are authoritative, accessible, and enriched with easily understandable figures, tables, and other display items. The goal is to provide an unparalleled service to authors, referees, and readers, and the journal works diligently to maximize the usefulness and impact of each article. Nature Reviews Molecular Cell Biology publishes a variety of article types, including Reviews, Perspectives, Comments, and Research Highlights, all of which are relevant to molecular and cell biologists. The journal's broad scope ensures that the articles it publishes reach the widest possible audience.
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