McCarthy J E
Posttranscriptional Control Group, Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology (UMIST), Manchester M60 1QD, United Kingdom.
Microbiol Mol Biol Rev. 1998 Dec;62(4):1492-553. doi: 10.1128/MMBR.62.4.1492-1553.1998.
Studies of the budding yeast Saccharomyces cerevisiae have greatly advanced our understanding of the posttranscriptional steps of eukaryotic gene expression. Given the wide range of experimental tools applicable to S. cerevisiae and the recent determination of its complete genomic sequence, many of the key challenges of the posttranscriptional control field can be tackled particularly effectively by using this organism. This article reviews the current knowledge of the cellular components and mechanisms related to translation and mRNA decay, with the emphasis on the molecular basis for rate control and gene regulation. Recent progress in characterizing translation factors and their protein-protein and RNA-protein interactions has been rapid. Against the background of a growing body of structural information, the review discusses the thermodynamic and kinetic principles that govern the translation process. As in prokaryotic systems, translational initiation is a key point of control. Modulation of the activities of translational initiation factors imposes global regulation in the cell, while structural features of particular 5' untranslated regions, such as upstream open reading frames and effector binding sites, allow for gene-specific regulation. Recent data have revealed many new details of the molecular mechanisms involved while providing insight into the functional overlaps and molecular networking that are apparently a key feature of evolving cellular systems. An overall picture of the mechanisms governing mRNA decay has only very recently begun to develop. The latest work has revealed new information about the mRNA decay pathways, the components of the mRNA degradation machinery, and the way in which these might relate to the translation apparatus. Overall, major challenges still to be addressed include the task of relating principles of posttranscriptional control to cellular compartmentalization and polysome structure and the role of molecular channelling in these highly complex expression systems.
对出芽酵母酿酒酵母的研究极大地推动了我们对真核基因表达转录后步骤的理解。鉴于适用于酿酒酵母的广泛实验工具以及其完整基因组序列的近期测定，转录后控制领域的许多关键挑战可以通过使用这种生物体得到特别有效的解决。本文综述了与翻译和mRNA降解相关的细胞成分和机制的当前知识，重点是速率控制和基因调控的分子基础。在表征翻译因子及其蛋白质-蛋白质和RNA-蛋白质相互作用方面，近期进展迅速。在不断增加的结构信息背景下，本文讨论了支配翻译过程的热力学和动力学原理。与原核系统一样，翻译起始是控制的关键点。翻译起始因子活性的调节在细胞中施加全局调控，而特定5'非翻译区的结构特征，如上游开放阅读框和效应物结合位点，则允许进行基因特异性调控。近期数据揭示了所涉及分子机制的许多新细节，同时深入了解了功能重叠和分子网络，这显然是不断进化的细胞系统的一个关键特征。关于mRNA降解机制的整体图景直到最近才开始形成。最新研究揭示了有关mRNA降解途径、mRNA降解机制的组成成分以及它们与翻译装置可能的关联方式的新信息。总体而言，仍有待解决的主要挑战包括将转录后控制原理与细胞区室化和多核糖体结构相关联的任务，以及分子通道在这些高度复杂的表达系统中的作用。
