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

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 and Silvi Rouskin ()
Additional contact information
Tammy C. T. Lan: Whitehead Institute for Biomedical Research
Matty F. Allan: Whitehead Institute for Biomedical Research
Lauren E. Malsick: National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, Boston University
Jia Z. Woo: Whitehead Institute for Biomedical Research
Chi Zhu: University of California
Fengrui Zhang: Whitehead Institute for Biomedical Research
Stuti Khandwala: Whitehead Institute for Biomedical Research
Sherry S. Y. Nyeo: Whitehead Institute for Biomedical Research
Yu Sun: Yale University School of Medicine
Junjie U. Guo: Yale University School of Medicine
Mark Bathe: Massachusetts Institute of Technology
Anders Näär: University of California
Anthony Griffiths: National Emerging Infectious Diseases Laboratories, Boston University School of Medicine, Boston University
Silvi Rouskin: Whitehead Institute for Biomedical Research

Nature Communications, 2022, vol. 13, issue 1, 1-14

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

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-28603-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28603-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-28603-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().