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SARS-CoV-2 Nsp1 binds the ribosomal mRNA channel to inhibit translation.
Schubert, Katharina; Karousis, Evangelos D; Jomaa, Ahmad; Scaiola, Alain; Echeverria, Blanca; Gurzeler, Lukas-Adrian; Leibundgut, Marc; Thiel, Volker; Mühlemann, Oliver; Ban, Nenad.
  • Schubert K; Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
  • Karousis ED; Department of Chemistry and Biochemistry, University of Bern, Bern, Switzerland.
  • Jomaa A; Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
  • Scaiola A; Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
  • Echeverria B; Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
  • Gurzeler LA; Department of Chemistry and Biochemistry, University of Bern, Bern, Switzerland.
  • Leibundgut M; Department of Biology, Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland.
  • Thiel V; Institute of Virology and Immunology, Bern, Switzerland.
  • Mühlemann O; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Ban N; Department of Chemistry and Biochemistry, University of Bern, Bern, Switzerland. oliver.muehlemann@dcb.unibe.ch.
Nat Struct Mol Biol ; 27(10): 959-966, 2020 10.
Article in English | MEDLINE | ID: covidwho-752470
Preprint
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Semantic information from SemMedBD (by NLM)
1. Synapsin I INTERACTS_WITH Protein Subunits
Subject
Synapsin I
Predicate
INTERACTS_WITH
Object
Protein Subunits
2. Proteins DISRUPTS mRNA binding
Subject
Proteins
Predicate
DISRUPTS
Object
mRNA binding
3. Synapsin I AFFECTS Translational Repression
Subject
Synapsin I
Predicate
AFFECTS
Object
Translational Repression
4. Synapsin I INTERACTS_WITH Protein Subunits
Subject
Synapsin I
Predicate
INTERACTS_WITH
Object
Protein Subunits
5. Proteins DISRUPTS mRNA binding
Subject
Proteins
Predicate
DISRUPTS
Object
mRNA binding
6. Synapsin I AFFECTS Translational Repression
Subject
Synapsin I
Predicate
AFFECTS
Object
Translational Repression
ABSTRACT
The SARS-CoV-2 non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, suppresses host innate immune functions. By combining cryo-electron microscopy and biochemistry, we show that SARS-CoV-2 Nsp1 binds to the human 40S subunit in ribosomal complexes, including the 43S pre-initiation complex and the non-translating 80S ribosome. The protein inserts its C-terminal domain into the mRNA channel, where it interferes with mRNA binding. We observe translation inhibition in the presence of Nsp1 in an in vitro translation system and in human cells. Based on the high-resolution structure of the 40S-Nsp1 complex, we identify residues of Nsp1 crucial for mediating translation inhibition. We further show that the full-length 5' untranslated region of the genomic viral mRNA stimulates translation in vitro, suggesting that SARS-CoV-2 combines global inhibition of translation by Nsp1 with efficient translation of the viral mRNA to allow expression of viral genes.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Biosynthesis / RNA, Messenger / Viral Nonstructural Proteins / Betacoronavirus Type of study: Prognostic study Limits: Humans Language: English Journal: Nat Struct Mol Biol Journal subject: Molecular Biology Year: 2020 Document Type: Article Affiliation country: S41594-020-0511-8

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Biosynthesis / RNA, Messenger / Viral Nonstructural Proteins / Betacoronavirus Type of study: Prognostic study Limits: Humans Language: English Journal: Nat Struct Mol Biol Journal subject: Molecular Biology Year: 2020 Document Type: Article Affiliation country: S41594-020-0511-8