ArticleProceedings of the National Academy of Sciences of the United States of America2024
Inhibition of mRNA nuclear export promotes SARS-CoV-2 pathogenesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Conserved mRNP remodeling mechanism of the TREX-2.1 complex.Nucleic acids research · 2026Article
- Super-resolution atlas of SARS-CoV-2 infection reveals protease-dependent organelle maturation, dsRNA landscapes, and intracellular structural proteins.Nature communications · 2026Article
- Tripartite motif-containing 34 (TRIM34) protein interacts with the nucleocytoplasmic transport machinery and negatively modulates antiviral responses.PLoS pathogens · 2026Article
- SARS-CoV-2 and MERS-CoV disrupt host protein synthesis via nsp1 with differential effects on the integrated stress response.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Breaking barriers: Respiratory viral strategies targeting the host's nuclear pore complex and nuclear transport pathways.Molecular biology of the cell · 2026Review
- Structural adaptability of SARS-CoV-2 Nsp1 with the host network.European biophysics journal : EBJ · 2026Article
- Synthetic Integration of an FCS into Coronaviruses-Hype or an Unresolved Biorisk? An Integrative Analysis of DNA Repair, Cancer Research, Drug Development, and Escape Mutant Traits.Life (Basel, Switzerland) · 2026Article
- Strategic variations in sarbecovirus and merbecovirus Nsp1 linker regions for translation inhibition.Nucleic acids research · 2026Article
- SARS-CoV-2 and MERS-CoV disrupt host protein synthesis via nsp1 with differential effects on the integrated stress response.bioRxiv : the preprint server for biology · 2025Article
- Crystallographic fragment screening against SARS-CoV-2 nonstructural protein 1 using the F2X-Entry Screen and a newly developed fragment library.Acta crystallographica. Section D, Structural biology · 2025Article
- Structural mechanism of DDX39B regulation by human TREX-2 and a related complex in mRNP remodeling.Nature communications · 2025Article
- Review
- Cryo-EM structure of the CBC-ALYREF complex.eLife · 2024Article
- SARS-CoV-2 Nsp1 traps RNA in the nucleus to escape immune detection.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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18 authors.
Funding
Abstract
The nonstructural protein 1 (Nsp1) of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a virulence factor that targets multiple cellular pathways to inhibit host gene expression and antiviral response. However, the underlying mechanisms of the various Nsp1-mediated functions and their contributions to SARS-CoV-2 virulence remain unclear. Among the targets of Nsp1 is the mRNA (messenger ribonucleic acid) export receptor NXF1-NXT1, which mediates nuclear export of mRNAs from the nucleus to the cytoplasm. Based on Nsp1 crystal structure, we generated mutants on Nsp1 surfaces and identified an acidic N-terminal patch that is critical for interaction with NXF1-NXT1. Photoactivatable Nsp1 probe reveals the RNA Recognition Motif (RRM) domain of NXF1 as an Nsp1 N-terminal binding site. By mutating the Nsp1 N-terminal acidic patch, we identified a separation-of-function mutant of Nsp1 that retains its translation inhibitory function but substantially loses its interaction with NXF1 and reverts Nsp1-mediated mRNA export inhibition. We then generated a recombinant (r)SARS-CoV-2 mutant on the Nsp1 N-terminal acidic patch and found that this surface is key to promote NXF1 binding and inhibition of host mRNA nuclear export, viral replication, and pathogenicity in vivo. Thus, these findings provide a mechanistic understanding of Nsp1-mediated mRNA export inhibition and establish the importance of this pathway in the virulence of SARS-CoV-2.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.