Secondary structural ensembles of the SARS-CoV-2 RNA genome in infected cells
Name
s41467-022-28603-2.pdf
Description
Published version
Size
3.97 MB
Format
Adobe PDF
Checksum (MD5)
1f7cf59c3f43e5e54464ba9f17543b5a
Author(s)
Lan, Tammy CT
Allan, Matty F
Malsick, Lauren E
Woo, Jia Z
Zhu, Chi
Zhang, Fengrui
Khandwala, Stuti
Nyeo, Sherry SY
Sun, Yu
Guo, Junjie U
Date Issued
2022
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Lan, Tammy CT, Allan, Matty F, Malsick, Lauren E, Woo, Jia Z, Zhu, Chi et al. 2022. "Secondary structural ensembles of the SARS-CoV-2 RNA genome in infected cells." Nature Communications, 13 (1).
Version
Final published version
Abstract
AbstractSARS-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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1038/S41467-022-28603-2
