Journal
MOLECULAR CELL
Volume 80, Issue 6, Pages 1067-+Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2020.11.004
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Funding
- Cancer Research UK [C13474/A18583, C6946/A14492]
- Deutsche Forschungsgemeinschaft (DFG
- German Research Foundation) [197785619 SFB 1021]
- Wellcome grants [104640/Z/14/Z, 092096/Z/10/Z]
- RAPID consortium of Bundesministerium fur Bildung und Forschung (BMBF) [01KI1723E]
- MAD-CoV-2 consortium from the European Union's Horizon 2020 research and innovation program [101005026]
- Wellcome grant [207498/Z/17/Z]
- Wellcome Trust [207498/Z/17/Z, 104640/Z/14/Z, 092096/Z/10/Z] Funding Source: Wellcome Trust
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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-CoV2 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 longrange 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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