Structural and Functional Insights into Viral Programmed Ribosomal Frameshifting

Structural and Functional Insights into Viral Programmed Ribosomal Frameshifting
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DOI:
10.1146/annurev-virology-111821-120646
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发表时间:
2023-01-01
影响因子:
11.3
通讯作者:
Brierley, Ian
Brierley, Ian
中科院分区:
医学2区
文献类型:
--
作者:
Hill, Chris H.;Brierley, Ian

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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的准确翻译对所有生命都是必不可少的,翻译机制的自发错误非常罕见(类似于十万分之一的密码子)。程序性核糖体移码(programmed ribosomal frameshifting)是一种机制,其中延伸的核糖体被高频率地诱导,在确定的位置向后滑动一个核苷酸,并在新的阅读框中继续翻译。这被数百种RNA病毒利用作为翻译调节策略,它们依赖于基因组翻译来控制病毒蛋白的化学计量。虽然早期的研究集中在病毒学和生物化学方面,但X射线晶体学和冷冻电子显微镜(cryo-EM)的应用以及深度测序和单分子方法的出现揭示了意想不到的结构多样性和机制复杂性。分子球员从几个模型系统,现在已经详细的特点,无论是在隔离,最近,在延长核糖体的背景下。在这里,我们提供了一个最近的进展,并讨论在何种程度上仍然是一个有用的思维方式的一般模型。
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 (similar to 1/100,000 codons). Programmed ribosomal frameshifting ( 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 ofRNAviruses, which rely on during genome translation to control the stoichiometry of viral proteins. While early investigations of 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 remains a useful way of thinking.