Department of Physical Biochemistry, Max Planck Institute of Biophysical Chemistry, Goettingen, Germany.
Crit Rev Biochem Mol Biol. 2012 Jul-Aug;47(4):334-48. doi: 10.3109/10409238.2012.678284. Epub 2012 Apr 19.
Translation initiation is a crucial step of protein synthesis which largely defines how the composition of the cellular transcriptome is converted to the proteome and controls the response and adaptation to environmental stimuli. The efficiency of translation of individual mRNAs, and hence the basal shape of the proteome, is defined by the structures of the mRNA translation initiation regions. Initiation efficiency can be regulated by small molecules, proteins, or antisense RNAs, underscoring its importance in translational control. Although initiation has been studied in bacteria for decades, many aspects remain poorly understood. Recent evidence has suggested an unexpected diversity of pathways by which mRNAs can be recruited to the bacterial ribosome, the importance of structural dynamics of initiation intermediates, and the complexity of checkpoints for mRNA selection. In this review, we discuss how the ribosome shapes the landscape of translation initiation by non-linear kinetic processing of the transcriptome information. We summarize the major pathways by which mRNAs enter the ribosome depending on the structure of their 5' untranslated regions, the assembly and the structure of initiation intermediates, the individual and synergistic roles of initiation factors, and the mechanisms of mRNA and initiator tRNA selection.
翻译起始是蛋白质合成的关键步骤，在很大程度上决定了细胞转录组的组成如何转化为蛋白质组，并控制对环境刺激的反应和适应。单个 mRNA 的翻译效率，因此蛋白质组的基本形状，由 mRNA 翻译起始区的结构决定。起始效率可以通过小分子、蛋白质或反义 RNA 来调节，这凸显了其在翻译控制中的重要性。尽管几十年来一直在研究细菌中的起始，但仍有许多方面尚未得到很好的理解。最近的证据表明，mRNA 被招募到细菌核糖体的途径具有出乎意料的多样性，起始中间产物结构动力学的重要性，以及 mRNA 选择的检查点的复杂性。在这篇综述中，我们讨论了核糖体如何通过对转录组信息的非线性动力学处理来塑造翻译起始的景观。我们总结了根据 5'非翻译区的结构、起始中间产物的组装和结构、起始因子的单独和协同作用以及 mRNA 和起始 tRNA 选择的机制，mRNA 进入核糖体的主要途径。
