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Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection.
- Source :
-
Molecular cell [Mol Cell] 2021 Jul 01; Vol. 81 (13), pp. 2851-2867.e7. Date of Electronic Publication: 2021 May 24. - Publication Year :
- 2021
-
Abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 relies on cellular RNA-binding proteins (RBPs) to replicate and spread, although which RBPs control its life cycle remains largely unknown. Here, we employ a multi-omic approach to identify systematically and comprehensively the cellular and viral RBPs that are involved in SARS-CoV-2 infection. We reveal that SARS-CoV-2 infection profoundly remodels the cellular RNA-bound proteome, which includes wide-ranging effects on RNA metabolic pathways, non-canonical RBPs, and antiviral factors. Moreover, we apply a new method to identify the proteins that directly interact with viral RNA, uncovering dozens of cellular RBPs and six viral proteins. Among them are several components of the tRNA ligase complex, which we show regulate SARS-CoV-2 infection. Furthermore, we discover that available drugs targeting host RBPs that interact with SARS-CoV-2 RNA inhibit infection. Collectively, our results uncover a new universe of host-virus interactions with potential for new antiviral therapies against COVID-19.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- A549 Cells
COVID-19 genetics
Humans
Proteome genetics
RNA, Viral genetics
RNA-Binding Proteins genetics
Viral Proteins genetics
COVID-19 metabolism
Proteome metabolism
RNA, Viral metabolism
RNA-Binding Proteins metabolism
SARS-CoV-2 physiology
Viral Proteins metabolism
Virus Replication physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 81
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 34118193
- Full Text :
- https://doi.org/10.1016/j.molcel.2021.05.023