A conserved class of viral RNA structures regulate translation reinitiation through dynamic ribosome interactions.
A conserved class of viral RNA structures regulate translation reinitiation through dynamic ribosome interactions.
复制标题
一类保守的病毒 RNA 结构通过动态核糖体相互作用调节翻译重新启动。
DOI：
10.1101/2023.09.29.560040
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Kieft,JeffreyS
中科院分区：
文献类型：
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作者：
Sherlock,MadelineE;Langeberg,ConnerJ;Segar,KatherineE;Kieft,JeffreyS
某些病毒RNA编码其主要开放阅读框架下游的蛋白质，通过“终止-重新启动”事件表达。在某些情况下，位于这些病毒RNA中第一个终止密码子上游的结构与核糖体结合，抑制核糖体循环并诱导重新启动。我们使用生物信息学方法来识别新的病毒重新启动刺激RNA的例子，并通过实验验证了它们的二级结构和功能。我们用低温电子显微镜(Cryo-EM)确定了一个具有代表性的病毒RNA-核糖体复合体的结构。三维分类和变异性分析表明，病毒RNA结构可以在保持与核糖体连接的同时采样一系列构象，使核糖体能够在有限的mRNA序列范围内找到重新启动的起点。在冷冻-EM重建的背景下评估这一整个RNA类的保守特征和限制因素，有助于深入了解重新启动的机制，这是许多其他病毒和真核系统所采用的一种翻译调控策略。
Certain viral RNAs encode proteins downstream of their main open reading frame, expressed through "termination-reinitiation" events. In some cases, structures located upstream of the first stop codon within these viral RNAs bind the ribosome, inhibiting ribosome recycling and inducing reinitiation. We used bioinformatics methods to identify new examples of viral reinitiation-stimulating RNAs and experimentally verified their secondary structure and function. We determined the structure of a representative viral RNA-ribosome complex using cryoelectron microscopy (cryo-EM). 3D classification and variability analyses reveal that the viral RNA structure can sample a range of conformations while remaining tethered to the ribosome, enabling the ribosome to find a reinitiation start site within a limited range of mRNA sequence. Evaluating the conserved features and constraints of this entire RNA class within the context of the cryo-EM reconstruction provides insight into mechanisms enabling reinitiation, a translation regulation strategy employed by many other viral and eukaryotic systems.