ArticleRNA (New York, N.Y.)2022
The key features of SARS-CoV-2 leader and NSP1 required for viral escape of NSP1-mediated repression.
Article in RNA (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 62 citations in OpenAlex.
- Mechanism and key RNA determinants of SARS-CoV-2 Nsp1-induced endonucleolytic cleavage of mRNA.bioRxiv : the preprint server for biology · 2026Article
- Structure and sequence characteristics of 5'-stem-loop 1 modulate the escape from nsp1-mediated repression in SARS-CoV-2 variants.Nucleic acids research · 2026Article
- Structural adaptability of SARS-CoV-2 Nsp1 with the host network.European biophysics journal : EBJ · 2026Article
- Strategic variations in sarbecovirus and merbecovirus Nsp1 linker regions for translation inhibition.Nucleic acids research · 2026Article
- Targeting the SARS-CoV-2 RNA Translation Initiation Element SL1 by Molecules of Low Molecular Weight.Journal of the American Chemical Society · 2025Article
- Article
- The differential effect of SARS-CoV-2 NSP1 on mRNA translation and stability reveals new insights linking ribosome recruitment, codon usage, and virus evolution.Nucleic acids research · 2025Article
- Review
- The transcriptional and translational landscape of HCoV-OC43 infection.PLoS pathogens · 2025Article
- Article
- Inhibition of SARS-CoV-2 growth in the lungs of mice by a peptide-conjugated morpholino oligomer targeting viral RNA.Molecular therapy. Nucleic acids · 2024Article
- Comprehensive Profiling of Roquin Binding Preferences for RNA Stem-Loops.Angewandte Chemie (International ed. in English) · 2024Article
- SARS-CoV2 Nsp1 is a metal-dependent DNA and RNA endonuclease.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Article
- The emerging role of SARS-CoV-2 nonstructural protein 1 (nsp1) in epigenetic regulation of host gene expression.FEMS microbiology reviews · 2024Review
- Ribosome stalling duringPNAS nexus · 2024Article
- The Beak of Eukaryotic Ribosomes: Life, Work and Miracles.Biomolecules · 2024Review
- The 5'-terminal stem-loop RNA element of SARS-CoV-2 features highly dynamic structural elements that are sensitive to differences in cellular pH.Nucleic acids research · 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
- Characterization of nsp1 Binding to the Viral RNA Leader Sequence of Severe Acute Respiratory Syndrome Coronavirus.Biochemistry · 2024Article
- Evolution and Impact of Nucleic Acid Amplification Test (NAAT) for Diagnosis of Coronavirus Disease.Analytical chemistry · 2024Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SARS-CoV-2, responsible for the ongoing global pandemic, must overcome a conundrum faced by all viruses. To achieve its own replication and spread, it simultaneously depends on and subverts cellular mechanisms. At the early stage of infection, SARS-CoV-2 expresses the viral nonstructural protein 1 (NSP1), which inhibits host translation by blocking the mRNA entry tunnel on the ribosome; this interferes with the binding of cellular mRNAs to the ribosome. Viral mRNAs, on the other hand, overcome this blockade. We show that NSP1 enhances expression of mRNAs containing the SARS-CoV-2 leader. The first stem-loop (SL1) in the viral leader is both necessary and sufficient for this enhancement mechanism. Our analysis pinpoints specific residues within SL1 (three cytosine residues at the positions 15, 19, and 20) and another within NSP1 (R124), which are required for viral evasion, and thus might present promising drug targets. We target SL1 with the antisense oligo (ASO) to efficiently and specifically down-regulate SARS-CoV-2 mRNA. Additionally, we carried out analysis of a functional interactome of NSP1 using BioID and identified components of antiviral defense pathways. Our analysis therefore suggests a mechanism by which NSP1 inhibits the expression of host genes while enhancing that of viral RNA. This analysis helps reconcile conflicting reports in the literature regarding the mechanisms by which the virus avoids NSP1 silencing.
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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 OpenQuestion graph.