Secondary structural ensembles of the SARS-CoV-2 RNA genome in infected cells

• DOI: 10.1038/s41467-022-28603-2
• Publication Date: 2022-03-02T11:02:54Z
• Authors: Tammy C. T. Lan; Matty F. Allan; Lauren E. Malsick; Jia Z. Woo; Chi Zhu; Fengrui Zhang; Stuti Khandwala; Sherry S. Y. Nyeo; Yu Sun; Junjie U. Guo; Mark Bathe; Anders Näär; Anthony Griffiths; Silvi Rouskin
• Keywords: Coronavirus; Nucleic acid structure; Coronaviridae

SARS-CoV-2 is a betacoronavirus with single-stranded, positive-sense, 30-kilobase RNA genome responsible for the ongoing COVID-19 pandemic. Although population average structure models of were recently reported, there little experimental data on native structural ensembles, and most structures lack functional characterization. Here we report secondary heterogeneity entire in two lines infected cells at single nucleotide resolution. Our results reveal alternative conformations across critical frameshifting stimulation element (FSE) that are drastically different from prevailing models. Importantly, find this ensemble promotes rates much higher than canonical minimal FSE similar to ribosome profiling studies. highlight value studying its full length cellular context. The genomic detailed here lay groundwork coronavirus biology will guide design RNA-based therapeutics.