{
  "abstract": "MDA5 is an innate immune RNA sensor that senses infection with a range of viruses and other pathogens. MDA5's RNA agonists are not well defined. Here we used single-nucleotide resolution crosslinking and immunoprecipitation (iCLIP) to study its ligands. Of note, upon infection with SARS-CoV-2 or encephalomyocarditis virus, MDA5 bound overwhelmingly to cellular RNAs. Many binding sites were intronic and proximal to Alu elements and to potentially base-paired structures. Concomitantly, cytoplasmic levels of aberrant transcripts and intron-containing unspliced transcripts increased in infected cells and displayed enrichment of MDA5 iCLIP peaks. Moreover, overexpression of the splicing factor SRSF3 reduced aberrant transcription and abrogated MDA5 activation. Taken together, we propose that MDA5 surveys RNA processing fidelity and can detect infections by sensing perturbations of post-transcriptional events such as splicing.",
  "abstract_shown": true,
  "affiliations": [
    "Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia. natalia.sampaio@hudson.org.au",
    "Department of Molecular and Translational Sciences, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia. natalia.sampaio@hudson.org.au",
    "Medical Research Council Translational Immune Discovery Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. natalia.sampaio@hudson.org.au",
    "Medical Research Council Translational Immune Discovery Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK",
    "Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia",
    "Department of Molecular and Translational Sciences, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia",
    "RNA viruses and metabolism team, Institut de Recherche en Infectiologie de Montpellier (IRIM), CNRS, University of Montpellier, Montpellier, France",
    "IMol Polish Academy of Sciences, Warsaw, Poland",
    "Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia",
    "Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Natália G. Sampaio",
      "orcid": "0000-0002-8396-1354"
    },
    {
      "affs": [
        3
      ],
      "name": "Tanja Davis",
      "orcid": "0000-0003-4572-3467"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Linden J. Gearing",
      "orcid": "0000-0003-3508-3056"
    },
    {
      "affs": [
        3
      ],
      "name": "Antônio Gregorio Dias",
      "orcid": "0000-0003-4392-4206"
    },
    {
      "affs": [
        6
      ],
      "name": "Lise Chauveau",
      "orcid": "0000-0002-2671-4488"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Georgie Wray‐McCann",
      "orcid": "0009-0005-3156-9392"
    },
    {
      "affs": [
        3
      ],
      "name": "Valerie Odon",
      "orcid": "0000-0002-2811-6916"
    },
    {
      "affs": [
        7
      ],
      "name": "Vladyslava Liudkovska",
      "orcid": "0000-0002-0078-1041"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Alexandra L. McAllan",
      "orcid": "0000-0002-8545-8285"
    },
    {
      "affs": [
        3
      ],
      "name": "Chiara Cursi",
      "orcid": "0000-0002-9027-0789"
    },
    {
      "affs": [
        3
      ],
      "name": "Alice Mayer",
      "orcid": "0000-0002-6859-0612"
    },
    {
      "affs": [
        8,
        5
      ],
      "name": "Madara Ratnadiwakara",
      "orcid": "0000-0001-7252-1823"
    },
    {
      "affs": [
        8,
        5,
        9
      ],
      "name": "Minna‐Liisa Änkö",
      "orcid": "0000-0003-0446-3566"
    },
    {
      "affs": [
        7
      ],
      "name": "Maciej Cieśla",
      "orcid": "0000-0002-8460-1991"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Paul J. Hertzog",
      "orcid": "0000-0002-1373-8472"
    },
    {
      "affs": [
        3
      ],
      "name": "Jan Rehwinkel",
      "orcid": "0000-0003-3841-835X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0wnm94y0vb6jp.bib",
  "cited_by": 5,
  "doi": "10.1038/s41590-026-02614-3",
  "fulltext_url": null,
  "id": "0wnm94y0vb6jp",
  "issns": [
    "1529-2908",
    "1529-2916"
  ],
  "landing_url": "https://hal.science/hal-05778159v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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  "pdf_url": null,
  "pmcid": "PMC13506345",
  "pmid": "42581186",
  "published": "2026-08-11",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/0wnm94y0vb6jp.ris",
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    {
      "first_seen": "2026-10-30T12:17:47Z",
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  "subjects": [
    {
      "field": "biology",
      "origin": "hal:1.sdv.imm",
      "subfield": "immunology"
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  ],
  "title": "Loss of cellular RNA homeostasis contributes to MDA5 activation during virus infection",
  "title_text": "Loss of cellular RNA homeostasis contributes to MDA5 activation during virus infection",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:46Z",
  "url": "https://research.draconitic.com/paper/0wnm94y0vb6jp",
  "venue": "Nature Immunology",
  "versions": []
}