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The short- and long-range RNA Interactome of SARS-CoV-2

ABSTRACT: The Coronaviridae are 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 genome 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 long-range RNA interactome of the full-length SARS-CoV-2 genome and the subgenomic mRNAs. We uncover a network of RNA-RNA interactions spanning tens of thousands of nucleotides that facilitate the unique transcription mode of coronaviruses, and reveal that the viral genome adopts alternative topologies inside cells and undergoes genome cyclization. Moreover, we discover long RNA-bridges between adjacent open reading frames that encircle the programmed ribosomal frame-shifting element, and demonstrate their conservation in vivo for the related MERS-CoV. Finally, the SARS-CoV-2 genome and subgenomic mRNAs engage in different sets of interactions with cellular RNAs. Our findings illuminate RNA-based mechanisms governing replication, discontinuous transcription, and translation of coronaviruses, and will aid future efforts to develop antiviral strategies.

ORGANISM(S): Chlorocebus pygerythrus Homo sapiens

PROVIDER: GSE154662 | GEO | 2020/10/21

REPOSITORIES: GEO

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