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SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses.
Banerjee, Abhik K; Blanco, Mario R; Bruce, Emily A; Honson, Drew D; Chen, Linlin M; Chow, Amy; Bhat, Prashant; Ollikainen, Noah; Quinodoz, Sofia A; Loney, Colin; Thai, Jasmine; Miller, Zachary D; Lin, Aaron E; Schmidt, Madaline M; Stewart, Douglas G; Goldfarb, Daniel; De Lorenzo, Giuditta; Rihn, Suzannah J; Voorhees, Rebecca M; Botten, Jason W; Majumdar, Devdoot; Guttman, Mitchell.
Afiliación
  • Banerjee AK; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
  • Blanco MR; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Bruce EA; Departments of Medicine, Division of Immunobiology and Microbiology, and Molecular Genetics, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA.
  • Honson DD; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Chen LM; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Chow A; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Bhat P; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Ollikainen N; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Quinodoz SA; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Loney C; MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow G61 1QH, UK.
  • Thai J; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Miller ZD; Department of Surgery and University of Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT 05405, USA.
  • Lin AE; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Schmidt MM; Departments of Medicine, Division of Immunobiology and Microbiology, and Molecular Genetics, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA.
  • Stewart DG; MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow G61 1QH, UK.
  • Goldfarb D; MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow G61 1QH, UK.
  • De Lorenzo G; MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow G61 1QH, UK.
  • Rihn SJ; MRC-University of Glasgow Centre for Virus Research (CVR), Glasgow G61 1QH, UK.
  • Voorhees RM; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Botten JW; Departments of Medicine, Division of Immunobiology and Microbiology, and Molecular Genetics, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA.
  • Majumdar D; Department of Surgery and University of Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT 05405, USA. Electronic address: dev.Majumdar@med.uvm.edu.
  • Guttman M; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: mguttman@caltech.edu.
Cell ; 183(5): 1325-1339.e21, 2020 11 25.
Article en En | MEDLINE | ID: mdl-33080218
ABSTRACT
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biosíntesis de Proteínas / Empalme del ARN / Proteínas no Estructurales Virales / Interacciones Huésped-Patógeno / SARS-CoV-2 / COVID-19 Límite: Animals / Humans Idioma: En Revista: Cell Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biosíntesis de Proteínas / Empalme del ARN / Proteínas no Estructurales Virales / Interacciones Huésped-Patógeno / SARS-CoV-2 / COVID-19 Límite: Animals / Humans Idioma: En Revista: Cell Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos