Ribosome-induced RNA conformational changes in a viral 3'-UTR sense and regulate translation levels.

Ribosome-induced RNA conformational changes in a viral 3'-UTR sense and regulate translation levels.
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DOI:
10.1038/s41467-018-07542-x
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发表时间:
2018-11-29
影响因子:
16.6
通讯作者:
Kieft JS
Kieft JS
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hartwick EW;Costantino DA;MacFadden A;Nix JC;Tian S;Das R;Kieft JS

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结构化的RNA元件、程序化的RNA构象变化以及不同RNA结构域之间的相互作用是许多调节基因表达的模式的基础,要求研究理解支配这些现象的基本原理。通过对病毒RNA的3′非翻译区(UTR)结构的研究,我们发现3′非翻译区的不同背景赋予了不同的能力来增强相关开放阅读框的翻译。在一种情况下,核糖体诱导的构象变化的“传感器”RNA结构域影响一个单独的RNA的“功能”域,改变翻译效率。整个3′-UTR的结构揭示了结构上不同的结构域使用连续堆叠的碱基和支柱样接头的脊柱来创建用于在更高级结构内进行通信的管道。因此,这个3′-UTR RNA说明了RNA如何使用程序化的构象变化来感知上游开放阅读框的翻译状态,然后通过将该信息传递给其他RNA元件来产生调谐的功能反应。复杂的RNA三维结构经历功能上重要的程序化构象变化。在这里,作者报告了病毒3′-UTR内的两个结构和功能上偶联的RNA结构域如何通过构象变化感知核糖体,并通过调节翻译作出反应。
Structured RNA elements, programmed RNA conformational changes, and interactions between different RNA domains underlie many modes of regulating gene expression, mandating studies to understand the foundational principles that govern these phenomena. Exploring the structured 3′ untranslated region (UTR) of a viral RNA, we discovered that different contexts of the 3′-UTR confer different abilities to enhance translation of an associated open reading frame. In one context, ribosome-induced conformational changes in a ‘sensor’ RNA domain affect a separate RNA ‘functional’ domain, altering translation efficiency. The structure of the entire 3′-UTR reveals that structurally distinct domains use a spine of continuously stacked bases and a strut-like linker to create a conduit for communication within the higher-order architecture. Thus, this 3′-UTR RNA illustrates how RNA can use programmed conformational changes to sense the translation status of an upstream open reading frame, then create a tuned functional response by communicating that information to other RNA elements. Complex RNA three-dimensional structures undergo functionally important programmed conformational changes. Here, the authors report how two structurally and functionally coupled RNA domains within a viral 3′-UTR sense the ribosome through conformational changes and respond by modulating translation.
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