SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses | Zendy

Abhik K. Banerjee | Zendy; Mario R. Blanco | Zendy; Emily A. Bruce | Zendy; Drew D. Honson | Zendy; Linlin M. Chen | Zendy; Amy Chow | Zendy; Prashant Bhat | Zendy; Noah Ollikainen | Zendy; Sofia A. Quinodoz | Zendy; Colin Loney | Zendy; Jasmine Thai | Zendy; Zachary D. Miller | Zendy; Aaron E. Lin | Zendy; Madaline M. Schmidt | Zendy; Douglas G. Stewart | Zendy; Daniel Goldfarb | Zendy; Giuditta De Lorenzo | Zendy; Suzannah J. Rihn | Zendy; Rebecca M. Voorhees | Zendy; Jason Botten | Zendy; Devdoot Majumdar | Zendy; Mitchell Guttman | Zendy

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SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses

Author(s) -

Abhik K. Banerjee,

Mario R. Blanco,

Emily A. Bruce,

Drew D. Honson,

Linlin M. Chen,

Amy Chow,

Prashant Bhat,

Noah Ollikainen,

Sofia A. Quinodoz,

Colin Loney,

Jasmine Thai,

Zachary D. Miller,

Aaron E. Lin,

Madaline M. Schmidt,

Douglas G. Stewart,

Daniel Goldfarb,

Giuditta De Lorenzo,

Suzannah J. Rihn,

Rebecca M. Voorhees,

Jason Botten,

Devdoot Majumdar,

Mitchell Guttman

Publication year - 2020

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2020.10.004

Subject(s) - biology , rna splicing , translation (biology) , rna , coronavirus , messenger rna , rna binding protein , ribosome , microbiology and biotechnology , interferon , coronaviridae , virology , gene , genetics , disease , covid-19 , medicine , pathology , infectious disease (medical specialty)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus that causes the respiratory disease known as coronavirus disease 2019 (COVID-19). Despite the urgent need, we still do not fully understand the molecular basis of SARS-CoV-2 pathogenesis. Here, we comprehensively define the interactions between SARS-CoV-2 proteins and human RNAs. NSP16 binds to the mRNA recognition domains of the U1 and U2 splicing RNAs and acts to suppress global mRNA splicing upon SARS-CoV-2 infection. NSP1 binds to 18S ribosomal RNA in the mRNA entry channel of the ribosome and leads to global inhibition of mRNA translation upon infection. Finally, NSP8 and NSP9 bind to the 7SL RNA in the signal recognition particle and interfere with protein trafficking to the cell membrane upon infection. Disruption of each of these essential cellular functions acts to suppress the interferon response to viral infection. Our results uncover a multipronged strategy utilized by SARS-CoV-2 to antagonize essential cellular processes to suppress host defenses.

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