{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yuan S"],"funding":["Yale University","NIDA NIH HHS","U.S. Department of Defense","NCI NIH HHS","National Institutes of Health","US Department of Defense"],"pagination":["1055-1066.e6"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7833686"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["80(6)"],"pubmed_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."],"journal":["Molecular cell"],"pubmed_title":["Nonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNA."],"pmcid":["PMC7833686"],"funding_grant_id":["DP2 CA238295","DP2CA238295","RF1 DA048811","PR201784","U54CA209992-8697","R33CA225498","RF1DA048811","W81XWH2010072","R01 CA231112","1R01CA231112","R33 CA225498"],"pubmed_authors":["Xiong Y","Yuan S","Hu Y","Devarkar SC","Shen Q","Park JJ","Lomakin IB","Wu S","Peng L","Chen S","Dong MB"],"additional_accession":[]},"is_claimable":false,"name":"Nonstructural Protein 1 of SARS-CoV-2 Is a Potent Pathogenicity Factor Redirecting Host Protein Synthesis Machinery toward Viral RNA.","description":"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.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Dec","modification":"2026-05-01T00:35:58.556Z","creation":"2021-02-21T04:10:16Z"},"accession":"S-EPMC7833686","cross_references":{"pubmed":["33188728"],"doi":["10.1016/j.molcel.2020.10.034"]}}