Your browser doesn't support javascript.
Nonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNA.
Yuan, Shuai; Peng, Lei; Park, Jonathan J; Hu, Yingxia; Devarkar, Swapnil C; Dong, Matthew B; Shen, Qi; Wu, Shenping; Chen, Sidi; Lomakin, Ivan B; Xiong, Yong.
  • Yuan S; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA.
  • Peng L; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Systems Biology Institute, Yale University, West Haven, CT 06516, USA.
  • Park JJ; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Systems Biology Institute, Yale University, West Haven, CT 06516, USA.
  • Hu Y; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA.
  • Devarkar SC; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA.
  • Dong MB; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Systems Biology Institute, Yale University, West Haven, CT 06516, USA.
  • Shen Q; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA.
  • Wu S; Department of Pharmacology, Yale University, West Haven, CT 06516, USA.
  • Chen S; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Systems Biology Institute, Yale University, West Haven, CT 06516, USA. Electronic address: sidi.chen@yale.edu.
  • Lomakin IB; Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: ivan.lomakin@yale.edu.
  • Xiong Y; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA. Electronic address: yong.xiong@yale.edu.
Mol Cell ; 80(6): 1055-1066.e6, 2020 12 17.
Article in English | MEDLINE | ID: covidwho-1009762
Semantic information from SemMedBD (by NLM)
1. Synapsin I PART_OF 2019 novel coronavirus
Subject
Synapsin I
Predicate
PART_OF
Object
2019 novel coronavirus
2. Synapsin I DISRUPTS Cells
Subject
Synapsin I
Predicate
DISRUPTS
Object
Cells
3. Transcriptome PART_OF Cells
Subject
Transcriptome
Predicate
PART_OF
Object
Cells
4. Synapsin I INTERACTS_WITH Transcriptome
Subject
Synapsin I
Predicate
INTERACTS_WITH
Object
Transcriptome
5. Protein complex PART_OF Ribosomes
Subject
Protein complex
Predicate
PART_OF
Object
Ribosomes
6. Virulence Factors PART_OF 2019 novel coronavirus
Subject
Virulence Factors
Predicate
PART_OF
Object
2019 novel coronavirus
7. Synapsin I PART_OF 2019 novel coronavirus
Subject
Synapsin I
Predicate
PART_OF
Object
2019 novel coronavirus
8. Synapsin I DISRUPTS Cells
Subject
Synapsin I
Predicate
DISRUPTS
Object
Cells
9. Transcriptome PART_OF Cells
Subject
Transcriptome
Predicate
PART_OF
Object
Cells
10. Synapsin I INTERACTS_WITH Transcriptome
Subject
Synapsin I
Predicate
INTERACTS_WITH
Object
Transcriptome
11. Protein complex PART_OF Ribosomes
Subject
Protein complex
Predicate
PART_OF
Object
Ribosomes
12. Virulence Factors PART_OF 2019 novel coronavirus
Subject
Virulence Factors
Predicate
PART_OF
Object
2019 novel coronavirus
ABSTRACT
The causative virus of the COVID-19 pandemic, SARS-CoV-2, uses its nonstructural protein 1 (Nsp1) to suppress cellular, but not viral, protein synthesis through yet unknown mechanisms. We show here that among all viral proteins, Nsp1 has the largest impact on host viability in the cells of human lung origin. Differential expression analysis of mRNA-seq data revealed that Nsp1 broadly alters the cellular transcriptome. Our cryo-EM structure of the Nsp1-40S ribosome complex shows that Nsp1 inhibits translation by plugging the mRNA entry channel of the 40S. We also determined the structure of the 48S preinitiation complex formed by Nsp1, 40S, and the cricket paralysis virus internal ribosome entry site (IRES) RNA, which shows that it is nonfunctional because of the incorrect position of the mRNA 3' region. Our results elucidate the mechanism of host translation inhibition by SARS-CoV-2 and advance understanding of the impacts from a major pathogenicity factor of SARS-CoV-2.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Biosynthesis / RNA, Messenger / RNA, Viral / Viral Nonstructural Proteins / SARS-CoV-2 / COVID-19 Limits: Animals / Humans Language: English Journal: Mol Cell Journal subject: Molecular Biology Year: 2020 Document Type: Article Affiliation country: J.molcel.2020.10.034

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Biosynthesis / RNA, Messenger / RNA, Viral / Viral Nonstructural Proteins / SARS-CoV-2 / COVID-19 Limits: Animals / Humans Language: English Journal: Mol Cell Journal subject: Molecular Biology Year: 2020 Document Type: Article Affiliation country: J.molcel.2020.10.034