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The N-terminal domain of SARS-CoV-2 nsp1 plays key roles in suppression of cellular gene expression and preservation of viral gene expression.
Mendez, Aaron S; Ly, Michael; González-Sánchez, Angélica M; Hartenian, Ella; Ingolia, Nicholas T; Cate, Jamie H; Glaunsinger, Britt A.
  • Mendez AS; Department of Plant & Microbial Biology, University of California, Berkeley, Berkeley, CA, USA.
  • Ly M; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
  • González-Sánchez AM; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA; Comparative Biochemistry Graduate Program, University of California, Berkeley, Berkeley, CA, USA.
  • Hartenian E; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
  • Ingolia NT; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA; California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA, USA.
  • Cate JH; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA; California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA; Department
  • Glaunsinger BA; Department of Plant & Microbial Biology, University of California, Berkeley, Berkeley, CA, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA; California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA, US
Cell Rep ; 37(3): 109841, 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1439922
ABSTRACT
Nonstructural protein 1 (nsp1) is a coronavirus (CoV) virulence factor that restricts cellular gene expression by inhibiting translation through blocking the mRNA entry channel of the 40S ribosomal subunit and by promoting mRNA degradation. We perform a detailed structure-guided mutational analysis of severe acute respiratory syndrome (SARS)-CoV-2 nsp1, revealing insights into how it coordinates these activities against host but not viral mRNA. We find that residues in the N-terminal and central regions of nsp1 not involved in docking into the 40S mRNA entry channel nonetheless stabilize its association with the ribosome and mRNA, both enhancing its restriction of host gene expression and enabling mRNA containing the SARS-CoV-2 leader sequence to escape translational repression. These data support a model in which viral mRNA binding functionally alters the association of nsp1 with the ribosome, which has implications for drug targeting and understanding how engineered or emerging mutations in SARS-CoV-2 nsp1 could attenuate the virus.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Gene Expression Regulation, Viral / Viral Nonstructural Proteins / SARS-CoV-2 / COVID-19 Limits: Female / Humans Language: English Journal: Cell Rep Year: 2021 Document Type: Article Affiliation country: J.celrep.2021.109841

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Gene Expression Regulation, Viral / Viral Nonstructural Proteins / SARS-CoV-2 / COVID-19 Limits: Female / Humans Language: English Journal: Cell Rep Year: 2021 Document Type: Article Affiliation country: J.celrep.2021.109841