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传播的病毒抗核酶RNA含有双循环结构

Conner J Langeberg^1,2, Matthew J Szucs¹, Madeline E Sherlock^1,3

¹Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Nature communications

|May 15, 2025

概括

弗拉维病毒使用称为xrRNAs的结构化RNA来抵抗宿主酶的降解. 这项研究揭示了Powasan Virus中独特的xrRNA结构,这是一种由传播的病原体,突出了病毒RNA保护的保存策略.

科学领域:

病毒学病毒学
结构生物学结构生物学
在RNA生物学,RNA生物学.

背景情况:

弗拉维病毒导致人类重大疾病.
亚基因组非编码RNAs,特别是抗外ibonucleaseRNAs (xrRNAs),对于弗拉维病毒复制至关重要.
以前解决的蚊子传播的黄斑病毒的xrRNA结构显示了一个保存的环状动图,但传播的黄斑病毒xrRNA在结构上仍然没有特征.

研究的目的:

为了调查波瓦桑病毒中的xrRNAs的存在和结构,一个传播的黄斑病毒.
阐明Powassan病毒xrRNA的三维折叠,并了解其对外核糖核酶的抵抗机制.
为了比较波瓦桑病毒xrRNA的结构特征与其他病毒的结构特征.

主要方法:

在Powassan病毒中检测和描述xrRNAs.
普瓦桑病毒xrRNA.RNA的二次结构分析.
低温电子显微镜 (cryo-EM) 用于确定普瓦桑病毒xrRNA的3D结构.
整合结构数据与协变分析和生物化学分析.

主要成果:

在Powassan病毒中确认了xrRNA的存在.
确定了普瓦桑病毒xrRNA的二次结构.
获得了中分辨率的冷EM图,显示了xrRNA结构中独特的双循环环元素.
开发了一个模型,显示保存的核心折叠,但在外核糖酶相互作用时重建的双循环环.

结论:

普瓦桑病毒利用一个独特的xrRNA结构,具有双循环环,具有对外核酶的耐药性.
这些发现揭示了Flaviviridae家族中病毒RNA保护的保存,但适应性,基于结构的策略.
这项工作提供了对弗拉维病毒病原体背后的分子机制的见解,并为抗病毒策略提供了潜在的目标.

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