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...
| প্রধান লেখক: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
Cell Press
2021
|
| _version_ | 1826311496913649664 |
|---|---|
| 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. |
| first_indexed | 2024-03-07T08:10:42Z |
| format | Journal article |
| id | oxford-uuid:2b1dbdf8-8da4-4b8d-a355-f996f061f7fb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:10:42Z |
| publishDate | 2021 |
| publisher | Cell Press |
| record_format | dspace |
| 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 |
| work_keys_str_mv | AT kamelw globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT noerenbergm globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT cerikanb globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT chenh globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT jarvelinai globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT kammounm globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT leejy globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT shuain globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT garciamorenom globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT andrejevaa globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT deerymj globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT johnsonn globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT neufeldtcj globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT cortesem globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT knightml globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT lilleyks globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT martinezj globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT davisi globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT bartenschlagerr globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT mohammeds globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection AT castelloa globalanalysisofproteinrnainteractionsinsarscov2infectedcellsrevealskeyregulatorsofinfection |