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Mol Cell . Comprehensive in vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms

tetano

Editor, Senior Moderator
Mol Cell


. 2021 Jan 1;S1097-2765(20)30962-X.
doi: 10.1016/j.molcel.2020.12.041. Online ahead of print.
Comprehensive in vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms


Nicholas C Huston[SUP] 1 [/SUP], Han Wan[SUP] 2 [/SUP], Madison S Strine[SUP] 3 [/SUP], Rafael de Cesaris Araujo Tavares[SUP] 4 [/SUP], Craig B Wilen[SUP] 3 [/SUP], Anna Marie Pyle[SUP] 5 [/SUP]



Affiliations

Abstract

Severe-acute-respiratory-syndrome-related coronavirus 2 (SARS-CoV-2) is the positive-sense RNA virus that causes coronavirus disease 2019 (COVID-19). The genome of SARS-CoV-2 is unique among viral RNAs in its vast potential to form RNA structures, yet as much as 97% of its 30 kilobases have not been structurally explored. Here, we apply a novel long amplicon strategy to determine the secondary structure of the SARS-CoV-2 RNA genome at single-nucleotide resolution in infected cells. Our in-depth structural analysis reveals networks of well-folded RNA structures throughout Orf1ab and reveals aspects of SARS-CoV-2 genome architecture that distinguish it from other RNA viruses. Evolutionary analysis shows that several features of the SARS-CoV-2 genomic structure are conserved across β-coronaviruses, and we pinpoint regions of well-folded RNA structure that merit downstream functional analysis. The native, secondary structure of SARS-CoV-2 presented here is a roadmap that will facilitate focused studies on the viral life cycle, facilitate primer design, and guide the identification of RNA drug targets against COVID-19.

Keywords: RNA genome; RNA motif; RNA secondary structure; RNA structure; RNA virus; SHAPE-MaP; chemical probing; coronavirus; locked nucleic acids; riboregulation.
 
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