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.

基因表达的调控是生命的基础。尽管基因表达转录调控的作用已经被研究了几十年，但在过去的二十年里，人们已经清楚基因表达的转录后调控（其中翻译调控是主要部分）同样重要。翻译可分为四个主要阶段：起始、延伸、终止和核糖体回收。翻译主要在其起始过程中受到控制，这一过程最终导致核糖体在起始密码子上定位有起始tRNA，从而准备好开始延长蛋白链。mRNA 翻译已成为开发创新疗法的强大工具，但复杂起始过程背后的详细机制仍不清楚。最近对酵母和哺乳动物的研究已经开始阐明这一过程的一些以前不清楚的方面。在这篇综述中，我们讨论了真核翻译起始及其在健康和疾病中的调节的知识现状。具体来说，我们重点关注理解 43S 前起始复合物组装过程及其通过 mRNA 5' 端帽结合复合物真核翻译起始因子 4F (eIF4F) 募集的最新进展。此外，我们还讨论了沿 mRNA 5' 非翻译区核糖体扫描和起始密码子选择的最新见解，最终导致 60S 大亚基的连接和 80S 起始复合物的形成。