The Short- and Long-Range RNA-RNA Interactome of SARS-CoV-2.
The Short- and Long-Range RNA-RNA Interactome of SARS-CoV-2.
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DOI：
10.1016/j.molcel.2020.11.004
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发表时间：
2020-12-17
期刊：
影响因子：
16
通讯作者：
Miska EA
中科院分区：
文献类型：
--
作者：
Ziv O;Price J;Shalamova L;Kamenova T;Goodfellow I;Weber F;Miska EA
冠状病毒科是一个正链RNA病毒家族，包括SARS-CoV-2，COVID-19大流行的病原体。冠状病毒具有自然界中最大的单链RNA基因组，严重依赖长距离RNA-RNA相互作用来调节病毒的转录和复制途径。在这里，我们通过实验绘制了全长SARS-CoV-2基因组和亚基因组mRNA的体内RNA-RNA相互作用组。我们发现了一个跨越数万个核苷酸的RNA-RNA相互作用网络。这些相互作用揭示了病毒基因组和亚基因组在细胞内采用替代拓扑结构，并与宿主RNA进行不同的相互作用。值得注意的是，我们发现了一个长距离的RNA-RNA相互作用，FSE拱，包围编程核糖体移码元件。FSE-拱在相关的MERS-CoV中是保守的，并且处于纯化选择下。我们的研究结果阐明了基于RNA结构的冠状病毒复制、不连续转录和翻译机制，并将有助于未来开发抗病毒策略。细胞内SARS-CoV-2基因组和亚基因组的全面RNA-RNA网络跨越数千个碱基的长距离结构导致动态拓扑结构宿主和病毒RNA之间的多位点特异性相互作用核糖体移码元件周围的拱形正在纯化选择冠状病毒使用RNA结构来调节其功能。Ziv等人确定了SARS-CoV-2基因组和细胞内亚基因组中沿着RNA-RNA相互作用的图谱，揭示了远端元件之间的长距离碱基配对、替代共存的RNA拓扑结构以及病毒和宿主RNA之间的相互作用，并提供了对冠状病毒作用模式的见解。
The Coronaviridae is a family of positive-strand RNA viruses that includes SARS-CoV-2, the etiologic agent of the COVID-19 pandemic. Bearing the largest single-stranded RNA genomes in nature, coronaviruses are critically dependent on long-distance RNA-RNA interactions to regulate the viral transcription and replication pathways. Here we experimentally mapped the in vivo RNA-RNA interactome of the full-length SARS-CoV-2 genome and subgenomic mRNAs. We uncovered a network of RNA-RNA interactions spanning tens of thousands of nucleotides. These interactions reveal that the viral genome and subgenomes adopt alternative topologies inside cells and engage in different interactions with host RNAs. Notably, we discovered a long-range RNA-RNA interaction, the FSE-arch, that encircles the programmed ribosomal frameshifting element. The FSE-arch is conserved in the related MERS-CoV and is under purifying selection. Our findings illuminate RNA structure-based mechanisms governing replication, discontinuous transcription, and translation of coronaviruses and will aid future efforts to develop antiviral strategies. Comprehensive RNA-RNA networks of the SARS-CoV-2 genome and subgenomes inside cells Long-range structures spanning thousands of bases resulting in dynamic topologies Multiple site-specific interactions between host and virus RNAs An arch around the ribosomal frameshifting element is under purifying selection Coronaviruses use RNA structure to regulate their function. Ziv et al. identified maps of RNA-RNA interactions along the SARS-CoV-2 genome and subgenomes inside cells, revealing long-range base-pairing between distal elements, alternative co-existing RNA topologies, and interactions between virus and host RNA and providing insights into the coronavirus modes of action.