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The architecture of the SARS-CoV-2 RNA genome inside virion

ABSTRACT: The coronavirus disease 2019 caused by SARS-CoV-2 has led to an unprecedented health crisis. However, to date, the architecture of the viral RNA genomes inside virions have not been observed because the interiors of viral particles are not visible, even using sophisticated Cryo-electron microscopy and tomography methods. Here, we devised a virion applicable RNA in situ conformation sequencing (RIC-seq) technology, named vRIC-seq, for probing viral RNA structures in intact virions. Using vRIC-seq, we successfully generated an RNA 3D interaction map for SARS-CoV-2 and observed many topologically isolated RNA domains. Based on the map, we reconstructed the whole genome structure of SARS-CoV-2, which revealed a fascinating “unentangled globule” conformation of this RNA genome. Our secondary structure model not only faithfully captured known RNA structural elements but also identified many previously unknown long-range duplexes and higher-order junctions with apparent biological impacts. Importantly, our structural model also enabled rapid screening of potent small interfering RNAs to target vulnerable regions of the SARS-CoV-2 RNA genome to against its infections in Vero cells. Thus, beyond illustrating an innovative method for characterizing the viral RNA structures present in intact virions of potentially any RNA virus and showing how this data can be quickly exploited to develop antiviral treatments, our work offers the first empirical-data-based look at how the SARS-CoV-2 RNA genome is organized inside virions.

ORGANISM(S): Severe acute respiratory syndrome coronavirus 2

PROVIDER: GSE155733 | GEO | 2021/03/25

REPOSITORIES: GEO

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