Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection.

Molecular Cell
Wael KamelAlfredo Castello

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.

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Citations

Sep 3, 2021·Nature Microbiology·Jim BaggenDirk Daelemans
Oct 17, 2021·Nature Communications·Jong Woo BaeJong-Seo Kim

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Software Mentioned

Sequence Read Archive
IRanges
package Variance Stabilizing Normalization “ VSN
STRING
package “
DEXSeq R package
GO
Hs
package “ DEP
package

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