{
  "abstract": "The coronavirus nucleocapsid (N) protein is indispensable for the viral lifecycle as part of the viral Replication-Transcription Complex together with Nsp3. Recent research demonstrated that phosphorylation of N by several host kinases intricately regulates its functions during infection. However, the mechanisms that control N dephosphorylation, and its physiological consequence, remain poorly understood. Here, we show that SARS-CoV-2 Nsp3 is a key orchestrator of N dephosphorylation by recruiting the phosphatase PP1/{gamma} via a conserved PP1-binding motif in the Ubl1 domain. Disruption of this motif abolishes N dephosphorylation and selectively impairs subgenomic RNA synthesis. Comparative interactome proteomics analysis of phospho-mimic vs. phospho-deficient N, together with functional validation, revealed that the host splicing factor SRSF1 cooperates with unphosphorylated N to promote subgenomic RNA transcription. These findings uncover an unrecognized mechanism in which Nsp3-guided N dephosphorylation by PP1/{gamma} enables coronavirus subgenomic RNA replication and highlight a potentially targetable axis for antiviral intervention.",
  "abstract_shown": true,
  "affiliations": [
    "Cleveland Clinic Florida Research and Innovation Center"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "J. Zhu"
    },
    {
      "name": "C. Chiang"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Gack"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/02wa09nm2r4q2.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.25.754410",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754410v1.full",
  "id": "02wa09nm2r4q2",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754410v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "2725|SARS-CoV-2 and COVID-19 Research"
    ]
  ],
  "openalex": "W7214471076",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754410v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/02wa09nm2r4q2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:41Z",
      "native_id": "10.64898/2026.09.25.754410",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754410v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Nsp3 Ubl1-orchestrated dephosphorylation of N protein promotes coronaviral subgenomic RNA synthesis",
  "title_text": "Nsp3 Ubl1-orchestrated dephosphorylation of N protein promotes coronaviral subgenomic RNA synthesis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:41Z",
  "url": "https://research.draconitic.com/paper/02wa09nm2r4q2",
  "venue": "bioRxiv",
  "versions": []
}