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

Ziv O et al. (2020) Molecular Cell. Advance online publication. DOI: 10.1016/j.molcel.2020.11.004.

• Watch the short video in which Omer Ziv describes this study
• Read the news story on the Unversity of Cambridge website

Abstract from the paper

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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Read our previous news story about the COMRADES technique used in this study, developed by Omer Ziv and colleagues and applied to Zika virus. Also described in this short YouTube video.

Read more about research in the Miska lab, and watch Eric Miska describe his research on YouTube.