EMBL-Australia Collaborating Group, Department of Genome Sciences, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
Victor Chang Cardiac Research Institute, Darlinghurst, Australia.
Wiley Interdiscip Rev RNA. 2018 Jul;9(4):e1473. doi: 10.1002/wrna.1473. Epub 2018 Apr 6.
Gene expression universally relies on protein synthesis, where ribosomes recognize and decode the messenger RNA template by cycling through translation initiation, elongation, and termination phases. All aspects of translation have been studied for decades using the tools of biochemistry and molecular biology available at the time. Here, we focus on the mechanism of translation initiation in eukaryotes, which is remarkably more complex than prokaryotic initiation and is the target of multiple types of regulatory intervention. The "consensus" model, featuring cap-dependent ribosome entry and scanning of mRNA leader sequences, represents the predominantly utilized initiation pathway across eukaryotes, although several variations of the model and alternative initiation mechanisms are also known. Recent advances in structural biology techniques have enabled remarkable molecular-level insights into the functional states of eukaryotic ribosomes, including a range of ribosomal complexes with different combinations of translation initiation factors that are thought to represent bona fide intermediates of the initiation process. Similarly, high-throughput sequencing-based ribosome profiling or "footprinting" approaches have allowed much progress in understanding the elongation phase of translation, and variants of them are beginning to reveal the remaining mysteries of initiation, as well as aspects of translation termination and ribosomal recycling. A current view on the eukaryotic initiation mechanism is presented here with an emphasis on how recent structural and footprinting results underpin axioms of the consensus model. Along the way, we further outline some contested mechanistic issues and major open questions still to be addressed. This article is categorized under: Translation > Translation Mechanisms Translation > Translation Regulation RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.
基因表达普遍依赖于蛋白质合成，核糖体通过循环经历翻译起始、延伸和终止阶段，识别和解码信使 RNA 模板。几十年来，人们一直使用当时可用的生物化学和分子生物学工具来研究翻译的各个方面。在这里，我们专注于真核生物翻译起始的机制，它比原核起始复杂得多，是多种类型调控干预的目标。“共识”模型，其特征是依赖帽结构的核糖体进入和 mRNA 前导序列的扫描，代表了真核生物中主要使用的起始途径，尽管也存在该模型的几种变体和替代起始机制。结构生物学技术的最新进展使人们能够对真核核糖体的功能状态进行惊人的分子水平洞察，包括一系列具有不同翻译起始因子组合的核糖体复合物，这些复合物被认为代表了起始过程的真实中间体。同样，基于高通量测序的核糖体图谱或“足迹”方法在理解翻译延伸阶段方面取得了很大进展，并且它们的变体开始揭示起始的其余奥秘，以及翻译终止和核糖体循环的方面。本文提出了目前对真核起始机制的看法，重点介绍了最近的结构和足迹结果如何支持共识模型的公理。在此过程中，我们进一步概述了一些有争议的机制问题和仍有待解决的主要问题。本文属于以下类别：翻译 > 翻译机制 翻译 > 翻译调控 RNA 与蛋白质和其他分子的相互作用 > 蛋白质-RNA 相互作用：功能意义
