tetano
Editor, Senior Moderator
Mol Cell
. 2021 May 24;S1097-2765(21)00407-X.
doi: 10.1016/j.molcel.2021.05.023. Online ahead of print.
Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection
Wael Kamel[SUP] 1 [/SUP], Marko Noerenberg[SUP] 1 [/SUP], Berati Cerikan[SUP] 2 [/SUP], Honglin Chen[SUP] 3 [/SUP], Aino I Järvelin[SUP] 3 [/SUP], Mohamed Kammoun[SUP] 4 [/SUP], Jeffrey Y Lee[SUP] 3 [/SUP], Ni Shuai[SUP] 4 [/SUP], Manuel Garcia-Moreno[SUP] 3 [/SUP], Anna Andrejeva[SUP] 5 [/SUP], Michael J Deery[SUP] 5 [/SUP], Natasha Johnson[SUP] 6 [/SUP], Christopher J Neufeldt[SUP] 2 [/SUP], Mirko Cortese[SUP] 2 [/SUP], Michael L Knight[SUP] 7 [/SUP], Kathryn S Lilley[SUP] 5 [/SUP], Javier Martinez[SUP] 8 [/SUP], Ilan Davis[SUP] 3 [/SUP], Ralf Bartenschlager[SUP] 9 [/SUP], Shabaz Mohammed[SUP] 10 [/SUP], Alfredo Castello[SUP] 11 [/SUP]
Affiliations
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.
Keywords: COVID-19; HSP90; RNA; RNA interactome; RNA-binding protein; SARS-CoV-2; antivirals; host-virus interactions; ribonucleoprotein; tRNA ligase; viral replication.
. 2021 May 24;S1097-2765(21)00407-X.
doi: 10.1016/j.molcel.2021.05.023. Online ahead of print.
Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection
Wael Kamel[SUP] 1 [/SUP], Marko Noerenberg[SUP] 1 [/SUP], Berati Cerikan[SUP] 2 [/SUP], Honglin Chen[SUP] 3 [/SUP], Aino I Järvelin[SUP] 3 [/SUP], Mohamed Kammoun[SUP] 4 [/SUP], Jeffrey Y Lee[SUP] 3 [/SUP], Ni Shuai[SUP] 4 [/SUP], Manuel Garcia-Moreno[SUP] 3 [/SUP], Anna Andrejeva[SUP] 5 [/SUP], Michael J Deery[SUP] 5 [/SUP], Natasha Johnson[SUP] 6 [/SUP], Christopher J Neufeldt[SUP] 2 [/SUP], Mirko Cortese[SUP] 2 [/SUP], Michael L Knight[SUP] 7 [/SUP], Kathryn S Lilley[SUP] 5 [/SUP], Javier Martinez[SUP] 8 [/SUP], Ilan Davis[SUP] 3 [/SUP], Ralf Bartenschlager[SUP] 9 [/SUP], Shabaz Mohammed[SUP] 10 [/SUP], Alfredo Castello[SUP] 11 [/SUP]
Affiliations
- PMID: 34118193
- DOI: 10.1016/j.molcel.2021.05.023
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.
Keywords: COVID-19; HSP90; RNA; RNA interactome; RNA-binding protein; SARS-CoV-2; antivirals; host-virus interactions; ribonucleoprotein; tRNA ligase; viral replication.