The Short- and Long-Range RNA-RNA Interactome of SARS-CoV-2

Abstract

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.

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Cited by papers we hold 5

• Secondary structural ensembles of the SARS-CoV-2 RNA genome in infected cells · 2022
  No notice
• Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions · 2021
  Not checked
• SARS-CoV-2: from its discovery to genome structure, transcription, and replication · 2021
  No notice
• The architecture of the SARS-CoV-2 RNA genome inside virion · 2021
  No notice
• Restriction of SARS-CoV-2 replication by targeting programmed −1 ribosomal frameshifting · 2021
  No notice

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