{
  "abstract": "RIG-I and MDA5 are cytosolic RNA sensors that recognize distinct viral ligands in mammals, yet RIG-I has been independently lost from multiple teleost lineages. How RIG-I-deficient vertebrates preserve recognition of RIG-I-associated viral RNA remains poorly understood. Here, we show that MDA5 from the large yellow croaker (Larimichthys crocea, Lc), a teleost species lacking RIG-I, recognizes both 5'-triphosphate dsRNA (5'ppp-dsRNA), the canonical ligand of RIG-I, and long dsRNA, the classical ligand of MDA5. Its C-terminal domain (CTD) is essential for the recognition of both ligands, with residues specifically required for sensing the 5'ppp moiety. Structural modeling, molecular dynamics simulations, and mutational validation support a model in which a flexible RNA-capping loop in the CTD confers LcMDA5 a conformational plasticity, allowing the CTD to cap the 5'ppp-dsRNA terminus for RIG-I-like recognition or orienting the CTD parallel to long-dsRNA axis for canonical MDA5 recognition. Disruption of 5'ppp recognition impaired LcMDA5-mediated antiviral activity against a RIG-I-sensitive virus. Downstream, LcMDA5 signals through an integrated MAVS-STING-TBK1/IRF3 axis to drive type I IFN responses to both RNA ligands. Our findings reveal an unexpectedly flexible architecture of vertebrate cytosolic RNA sensing in which a single RLR combines ligand-recognition and signaling properties classically partitioned between RIG-I and MDA5.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Mariculture Breeding, Key Laboratory of Marine Biotechnology of Fujian Province, College of Marine Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.",
    "Grupo de investigación en acuicultura (GIA), IU-ECOAQUA, Universidad De Las Palmas De Gran Canaria, Las Palmas, Spain.",
    "College of Biomedical Sciences, Fujian Agriculture and Forestry University, Fuzhou, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Wenxing Li",
      "orcid": "0000-0002-1084-0121"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuan Feng"
    },
    {
      "affs": [
        0
      ],
      "name": "Huazhi Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiamei Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Álvaro Fernández Montero",
      "orcid": "0000-0002-1997-0889"
    },
    {
      "affs": [
        2
      ],
      "name": "Jiangtao Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingqun Ao"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinhua Chen",
      "orcid": "0000-0003-2379-7596"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cy7v0ghnh3247.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.78318",
  "fulltext_url": "https://europepmc.org/articles/PMC13669214",
  "id": "cy7v0ghnh3247",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://europepmc.org/article/MED/42875852",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|interferon and immune responses"
    ]
  ],
  "openalex": "W7222052529",
  "pdf_url": "https://europepmc.org/articles/PMC13669214?pdf=render",
  "pmcid": "PMC13669214",
  "pmid": "42875852",
  "published": "2026-10-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cy7v0ghnh3247.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42875852",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42875852"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|interferon and immune responses",
      "subfield": "immunology"
    }
  ],
  "title": "A Fish MDA5 Integrates Canonical RIG-I and MDA5 Ligand Recognition.",
  "title_text": "A Fish MDA5 Integrates Canonical RIG-I and MDA5 Ligand Recognition.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/cy7v0ghnh3247",
  "venue": "Advanced science (Weinheim, Baden-Wurttemberg, Germany)",
  "versions": []
}