Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, USA
Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, USA.
RNA. 2023 Jul;29(7):865-884. doi: 10.1261/rna.079375.122. Epub 2023 Apr 6.
The gene expression pathway from DNA sequence to functional protein is not as straightforward as simple depictions of the central dogma might suggest. Each step is highly regulated, with complex and only partially understood molecular mechanisms at play. Translation is one step where the "one gene-one protein" paradigm breaks down, as often a single mature eukaryotic mRNA leads to more than one protein product. One way this occurs is through translation reinitiation, in which a ribosome starts making protein from one initiation site, translates until it terminates at a stop codon, but then escapes normal recycling steps and subsequently reinitiates at a different downstream site. This process is now recognized as both important and widespread, but we are only beginning to understand the interplay of factors involved in termination, recycling, and initiation that cause reinitiation events. There appear to be several ways to subvert recycling to achieve productive reinitiation, different types of stresses or signals that trigger this process, and the mechanism may depend in part on where the event occurs in the body of an mRNA. This perspective reviews the unique characteristics and mechanisms of reinitiation events, highlights the similarities and differences between three major scenarios of reinitiation, and raises outstanding questions that are promising avenues for future research.
从 DNA 序列到功能性蛋白质的基因表达途径并不像中心法则所暗示的那样简单直接。每一步都受到高度调控，其中涉及复杂且部分尚未被理解的分子机制。翻译是“一个基因对应一个蛋白质”这一范式崩溃的一个步骤，因为通常一个成熟的真核生物 mRNA 会产生不止一种蛋白质产物。发生这种情况的一种方式是通过翻译重新起始，其中核糖体从一个起始位点开始合成蛋白质，一直翻译直到在终止密码子处终止，但随后逃避正常的回收步骤，并随后在不同的下游位点重新起始。这个过程现在被认为既重要又普遍，但我们才刚刚开始理解终止、回收和起始中涉及的因素的相互作用，这些因素导致重新起始事件的发生。似乎有几种方法可以破坏回收以实现有效的重新起始，不同类型的应激或信号会触发这个过程，而且这个机制可能部分取决于事件发生在 mRNA 主体的哪个位置。这篇综述回顾了重新起始事件的独特特征和机制，强调了重新起始的三种主要情况之间的相似性和差异性，并提出了一些悬而未决的问题，这些问题是未来研究的有前景的方向。
