2. Academic Validation
  3. The Short- and Long-Range RNA-RNA Interactome of SARS-CoV-2

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

  • Mol Cell. 2020 Dec 17;80(6):1067-1077.e5. doi: 10.1016/j.molcel.2020.11.004.
Omer Ziv 1,  Jonathan Price 2,  Lyudmila Shalamova 3,  Tsveta Kamenova 2,  Ian Goodfellow 4,  Friedemann Weber 5,  Eric A Miska 6
Affiliations

Affiliations

  • 1 Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge CB2 1QN, UK. Electronic address: omer.ziv@gurdon.cam.ac.uk.
  • 2 Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge CB2 1QN, UK.
  • 3 Institute for Virology, FB10-Veterinary Medicine, Justus-Liebig University, 35392 Gießen, Germany.
  • 4 Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.
  • 5 Institute for Virology, FB10-Veterinary Medicine, Justus-Liebig University, 35392 Gießen, Germany. Electronic address: friedemann.weber@vetmed.uni-giessen.de.
  • 6 Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge CB2 1QN, UK; Wellcome Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK. Electronic address: eric.miska@gurdon.cam.ac.uk.
PMID: 33259809 DOI: 10.1016/j.molcel.2020.11.004
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.

Keywords

COMRADES; COVID-19; FSE-arch; RNA structure; RNA-RNA interaction; SARS-CoV-2; coronavirus; discontinuous transcription; host-virus; ribosomal frameshifting.

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