结结或不结结:SARS-CoV-2框架转移RNA元素的多种构造
Tamar Schlick1,2,3, Qiyao Zhu2, Abhishek Dey4
1Department of Chemistry, New York University, 100 Washington Square East, Silver Building, New York, New York 10003, United States.
Journal of the American Chemical Society
|July 20, 2021
概括
SARS-CoV-2 的框架转移 RNA 元素 (FSE) 使用了替代结构,而不仅仅是假设的 H 型伪结. 这些结构性见解揭示了COVID-19治疗的新治疗目标.
科学领域:
- 分子生物学
- 病毒学
- 结构生物学
背景情况:
- 通过调节开放阅读框架1a和1b之间的翻译,SARS-CoV-2的框架转移RNA元素 (FSE) 对病毒复制至关重要.
- 了解FSE的结构和动态是开发有效抗病毒疗法的关键.
- 之前的假设有利于FSE具有特定的三根H型伪结结构.
研究的目的:
- 调查SARS-CoV-2 FSE的结构格局和形态动态.
- 确定FSE在翻译过程中采用的替代RNA结构.
- 探索针对FSE结构重组的潜在治疗干预措施.
主要方法:
- 使用基于图形理论的RNA结构建模 ("RAG" - RNA-As-Graphs).
- 使用化学结构探测实验.
- 分析了全长的病毒基因组以确定竞争的结构动机.
主要成果:
- 在假定的H型假结 (3_6) 旁边,确定了一个可行的HL型三根假结 (3_3).
- 观察到一个未结合的三向结 RNA (3_5) 作为一个小的形状.
- 这些结构共享的茎1和3,在茎2的变化可能会调解核糖体相互作用和形状交换. 一个茎环图案 (2_2) 在全长基因组中竞争.
结论:
- 存在多种形式的SARS-CoV-2 FSE,挑战了之前的结构假设.
- FSE结构的变化,特别是Stem 2,与核糖体相互作用和移效率有关.
- 这些发现为病毒复制机制提供了洞察力,并突出了针对SARS-CoV-2的治疗干预的三个新途径.
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