{
  "abstract": "The SARS-CoV-2 nsp1 protein is a virulence factor that broadly inhibits cellular gene expression. Although cellular mRNAs are translationally inhibited by nsp1 and subsequently degraded, viral transcripts possess a 5' leader sequence (CoV2L) that enables them to escape nsp1-mediated repression. Both transcript targeting selectivity and mRNA decay require coordination by the nsp1 N-terminal domain (NTD) through an unknown mechanism. Here, we generated an alanine-scanning library of mutations encompassing all residues in the nsp1 NTD to gain a deeper understanding of how this domain coordinates nsp1 function. We screened this library for the ability to repress mRNA bearing a host- or CoV2L-derived 5' untranslated region, revealing two predominant clusters of residues required for target selectivity. These largely comprised adjacent surface-exposed beta-sheets on the NTD, whose deletion rendered CoV2L-containing mRNA susceptible to repression and prevented nsp1-induced mRNA decay. This work provides residue-level information on the role of the NTD in distinguishing among mRNA targets and further links nsp1 target selectivity to mRNA decay.",
  "abstract_shown": true,
  "affiliations": [
    "University of California, Berkeley"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "J. V. Guillen"
    },
    {
      "name": "S. A. Tokamov"
    },
    {
      "affs": [
        0
      ],
      "name": "B. A. Glaunsinger"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/96rf3fs0r7mzy.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.22.753304",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753304v1.full",
  "id": "96rf3fs0r7mzy",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753304v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "molecular biology"
    ],
    [
      "openalex",
      "2725|SARS-CoV-2 and COVID-19 Research"
    ]
  ],
  "openalex": "W7214150312",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753304v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/96rf3fs0r7mzy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:12Z",
      "native_id": "10.64898/2026.09.22.753304",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753304v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Mutational screening reveals a cluster of residues within the SARS-CoV-2 nsp1 N-terminus that confers RNA-targeting selectivity",
  "title_text": "Mutational screening reveals a cluster of residues within the SARS-CoV-2 nsp1 N-terminus that confers RNA-targeting selectivity",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:12Z",
  "url": "https://research.draconitic.com/paper/96rf3fs0r7mzy",
  "venue": "bioRxiv",
  "versions": []
}