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

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 ide...

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Egile Nagusiak: Kamel, W, Noerenberg, M, Cerikan, B, Chen, H, Järvelin, AI, Kammoun, M, Lee, JY, Shuai, N, Garcia-Moreno, M, Andrejeva, A, Deery, MJ, Johnson, N, Neufeldt, CJ, Cortese, M, Knight, ML, Lilley, KS, Martinez, J, Davis, I, Bartenschlager, R, Mohammed, S, Castello, A
Formatua: Journal article
Hizkuntza:English
Argitaratua: Cell Press 2021
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author Kamel, W
Noerenberg, M
Cerikan, B
Chen, H
Järvelin, AI
Kammoun, M
Lee, JY
Shuai, N
Garcia-Moreno, M
Andrejeva, A
Deery, MJ
Johnson, N
Neufeldt, CJ
Cortese, M
Knight, ML
Lilley, KS
Martinez, J
Davis, I
Bartenschlager, R
Mohammed, S
Castello, A
author_facet Kamel, W
Noerenberg, M
Cerikan, B
Chen, H
Järvelin, AI
Kammoun, M
Lee, JY
Shuai, N
Garcia-Moreno, M
Andrejeva, A
Deery, MJ
Johnson, N
Neufeldt, CJ
Cortese, M
Knight, ML
Lilley, KS
Martinez, J
Davis, I
Bartenschlager, R
Mohammed, S
Castello, A
author_sort Kamel, W
collection OXFORD
description 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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spelling oxford-uuid:2b1dbdf8-8da4-4b8d-a355-f996f061f7fb2023-11-30T07:56:44ZGlobal analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infectionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2b1dbdf8-8da4-4b8d-a355-f996f061f7fbEnglishSymplectic ElementsCell Press2021Kamel, WNoerenberg, MCerikan, BChen, HJärvelin, AIKammoun, MLee, JYShuai, NGarcia-Moreno, MAndrejeva, ADeery, MJJohnson, NNeufeldt, CJCortese, MKnight, MLLilley, KSMartinez, JDavis, IBartenschlager, RMohammed, SCastello, ASevere 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.
spellingShingle Kamel, W
Noerenberg, M
Cerikan, B
Chen, H
Järvelin, AI
Kammoun, M
Lee, JY
Shuai, N
Garcia-Moreno, M
Andrejeva, A
Deery, MJ
Johnson, N
Neufeldt, CJ
Cortese, M
Knight, ML
Lilley, KS
Martinez, J
Davis, I
Bartenschlager, R
Mohammed, S
Castello, A
Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection
title Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection
title_full Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection
title_fullStr Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection
title_full_unstemmed Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection
title_short Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection
title_sort global analysis of protein rna interactions in sars cov 2 infected cells reveals key regulators of infection
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