York Structural Biology Laboratory, York Biomedical Research Institute, Department of Biology, University of York, York, United Kingdom; email:
Department of Pathology, University of Cambridge, Cambridge, United Kingdom; email:
Annu Rev Virol. 2023 Sep 29;10(1):217-242. doi: 10.1146/annurev-virology-111821-120646. Epub 2023 Jun 20.
Protein synthesis by the ribosome is the final stage of biological information transfer and represents an irreversible commitment to gene expression. Accurate translation of messenger RNA is therefore essential to all life, and spontaneous errors by the translational machinery are highly infrequent (∼1/100,000 codons). Programmed -1 ribosomal frameshifting (-1PRF) is a mechanism in which the elongating ribosome is induced at high frequency to slip backward by one nucleotide at a defined position and to continue translation in the new reading frame. This is exploited as a translational regulation strategy by hundreds of RNA viruses, which rely on -1PRF during genome translation to control the stoichiometry of viral proteins. While early investigations of -1PRF focused on virological and biochemical aspects, the application of X-ray crystallography and cryo-electron microscopy (cryo-EM), and the advent of deep sequencing and single-molecule approaches have revealed unexpected structural diversity and mechanistic complexity. Molecular players from several model systems have now been characterized in detail, both in isolation and, more recently, in the context of the elongating ribosome. Here we provide a summary of recent advances and discuss to what extent a general model for -1PRF remains a useful way of thinking.
核糖体的蛋白质合成是生物信息传递的最后阶段，代表着基因表达的不可逆承诺。因此，信使 RNA 的准确翻译对于所有生命都是至关重要的，而翻译机制自发出现的错误非常罕见（约每 100,000 个密码子出现 1 次）。核糖体 -1 位移框（-1PRF）是一种机制，在此机制中，延伸中的核糖体在特定位置高频向后滑动一个核苷酸，并在新的阅读框中继续翻译。这是数以百计的 RNA 病毒利用的一种翻译调控策略，这些病毒依赖 -1PRF 在基因组翻译过程中控制病毒蛋白的化学计量。虽然 -1PRF 的早期研究集中在病毒学和生物化学方面，但 X 射线晶体学和低温电子显微镜（cryo-EM）的应用，以及深度测序和单分子方法的出现，揭示了出人意料的结构多样性和机制复杂性。现在已经详细描述了来自几个模型系统的分子参与者，无论是在分离状态下，还是最近在延伸核糖体的背景下。在这里，我们总结了最近的进展，并讨论了 -1PRF 的一般模型在多大程度上仍然是一种有用的思考方式。
