The SARS-CoV-2 RNA–protein interactome in infected human cells
Name
s41564-020-00846-z.pdf
Description
Published version
Size
4.02 MB
Format
Adobe PDF
Checksum (MD5)
dafc8c0b3b53cb6b512ee2cb47a88ba2
Author(s)
Schmidt, Nora
Lareau, Caleb A.
Keshishian, Hasmik
Ganskih, Sabina
Schneider, Cornelius
Hennig, Thomas
Melanson, Randy
Werner, Simone
Wei, Yuanjie
Zimmer, Matthias
Date Issued
December 2020
Journal
Nature Microbiology
Publisher
Springer Science and Business Media LLC
Citation
Schmidt, Nora et al. "The SARS-CoV-2 RNA–protein interactome in infected human cells." Nature Microbiology (December 2020): doi.org/10.1038/s41564-020-00846-z. © 2020 The Author(s)
Version
Final published version
Abstract
Characterizing the interactions that SARS-CoV-2 viral RNAs make with host cell proteins during infection can improve our understanding of viral RNA functions and the host innate immune response. Using RNA antisense purification and mass spectrometry, we identified up to 104 human proteins that directly and specifically bind to SARS-CoV-2 RNAs in infected human cells. We integrated the SARS-CoV-2 RNA interactome with changes in proteome abundance induced by viral infection and linked interactome proteins to cellular pathways relevant to SARS-CoV-2 infections. We demonstrated by genetic perturbation that cellular nucleic acid-binding protein (CNBP) and La-related protein 1 (LARP1), two of the most strongly enriched viral RNA binders, restrict SARS-CoV-2 replication in infected cells and provide a global map of their direct RNA contact sites. Pharmacological inhibition of three other RNA interactome members, PPIA, ATP1A1, and the ARP2/3 complex, reduced viral replication in two human cell lines. The identification of host dependency factors and defence strategies as presented in this work will improve the design of targeted therapeutics against SARS-CoV-2.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/s41564-020-00846-z
