The energy landscape of-1 ribosomal frameshifting
The energy landscape of-1 ribosomal frameshifting
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DOI：
10.1126/sciadv.aax6969
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发表时间：
2020-01-01
期刊：
影响因子：
13.6
通讯作者：
Puglisi, Joseph D.
中科院分区：
文献类型：
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作者：
Choi, Junhong;O'Loughlin, Sinead;Puglisi, Joseph D.
翻译阅读框架的维护确保了蛋白质合成过程中信息传递的保真度。然而，编码区内的程序性核糖体移码序列促进了预定位置的高读框变化率，从而丰富了基因组信息密度。移码通常是由3‘信使RNA(信使RNA)结构的存在刺激的，但这些信使RNA结构如何促进移码仍然存在争议。在这里，我们应用单分子和系综的方法来建立一个核糖体-1移码的机制模型。我们的模型表明，核糖体在移位之前本质上对移码很敏感，这种瞬时状态因存在精确定位的下游mRNA结构而延长。我们使用体内温度变化来挑战这一模型，这是根据体外结果做出的预测。我们的结果为分析其他移码增强子提供了一个定量的框架，并为利用程序化移码动态控制基因表达提供了一种潜在的方法。
Maintenance of translational reading frame ensures the fidelity of information transfer during protein synthesis. Yet, programmed ribosomal frameshifting sequences within the coding region promote a high rate of reading frame change at predetermined sites thus enriching genomic information density. Frameshifting is typically stimulated by the presence of 3' messenger RNA (mRNA) structures, but how these mRNA structures enhance -1 frameshifting remains debatable. Here, we apply single-molecule and ensemble approaches to formulate a mechanistic model of ribosomal -1 frameshifting. Our model suggests that the ribosome is intrinsically susceptible to frameshift before its translocation and this transient state is prolonged by the presence of a precisely positioned downstream mRNA structure. We challenged this model using temperature variation in vivo, which followed the prediction made based on in vitro results. Our results provide a quantitative framework for analyzing other frameshifting enhancers and a potential approach to control gene expression dynamically using programmed frameshifting.