{
  "abstract": "After excising an intron from pre-mRNA, the spliceosome remains trapped in a non-productive complex bound to the intron1–5. Termination of this complex is critical for spliceosome recycling and intron decay6, but the mechanism remains unknown. Here we present cryo-electron microscopy structures of human spliceosomes at two sequential stages of termination. First, the RNA helicases DHX15 and Aquarius unwind the RNA active site of the spliceosome, releasing bound components including U2 snRNA and extracting the buried intron–lariat branch point. The branch point is then debranched by the spliceosome-tethered enzyme DBR1, generating the previously unknown debranched intron spliceosome. This state recruits the RNA helicase DHX35 with its co-factors GPATCH1–WDR83, assisted by YJU2B. DHX35 ejects the debranched intron from the U6 snRNA–5′ splice site duplex, driving spliceosome disassembly and intron turnover. In defective spliceosomes stalled on aberrant introns, YJU2B partners with LENG1 to guide DHX35–GPATCH1–WDR83 for termination through spliceosome quality control. Together, we reveal the mechanism of regular spliceosome termination and its parallels with spliceosome quality control, ensuring accurate and efficient pre-mRNA splicing.",
  "abstract_shown": true,
  "affiliations": [
    "Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria",
    "Max Perutz Labs, Vienna BioCenter (VBC), Vienna, Austria",
    "University of Vienna, Max Perutz Labs, Vienna, Austria",
    "Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands",
    "Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, Vienna, Austria",
    "Andalusian Centre for Regenerative Medicine and Molecular Biology (CABIMER), Universidad de Sevilla-CSIC–Universidad Pablo de Olavide-Junta de Andalucía, Sevilla, Spain",
    "Departament of Cell Biology, Faculty of Biology, University of Sevilla, Sevilla, Spain"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Vytaute Boreikaite"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Rupert Faraway"
    },
    {
      "affs": [
        0
      ],
      "name": "Matthias K. Vorländer"
    },
    {
      "affs": [
        0
      ],
      "name": "Alexander W. Phillips",
      "orcid": "0000-0002-6689-9632"
    },
    {
      "affs": [
        0
      ],
      "name": "Leonie Opitz",
      "orcid": "0009-0001-9351-8620"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Moritz Wanke"
    },
    {
      "affs": [
        3
      ],
      "name": "George Yakoub",
      "orcid": "0000-0003-2727-7651"
    },
    {
      "affs": [
        1,
        2,
        4
      ],
      "name": "Gerald Raffl",
      "orcid": "0000-0003-0210-0286"
    },
    {
      "affs": [
        0
      ],
      "name": "Laura Fin"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Román González-Prieto",
      "orcid": "0000-0001-8997-2321"
    },
    {
      "affs": [
        3
      ],
      "name": "Martijn S. Luijsterburg"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Stefan L. Ameres",
      "orcid": "0000-0002-8248-3098"
    },
    {
      "affs": [
        0
      ],
      "name": "Clemens Plaschka",
      "orcid": "0000-0002-6020-9514"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4mynt7shc6zk1.bib",
  "cited_by": 0,
  "doi": "10.1038/s41586-026-11101-6",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13736545/",
  "id": "4mynt7shc6zk1",
  "issns": [
    "0028-0836",
    "1476-4687"
  ],
  "landing_url": "https://doi.org/10.1038/s41586-026-11101-6",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|RNA Research and Splicing"
    ]
  ],
  "openalex": "W7220848176",
  "pdf_url": null,
  "pmcid": "PMC13736545",
  "pmid": "42844479",
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4mynt7shc6zk1.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:21:58Z",
      "native_id": "PMC13736545",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41586-026-11101-6"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA Research and Splicing",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Mechanism of spliceosome termination",
  "title_text": "Mechanism of spliceosome termination",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:58Z",
  "url": "https://research.draconitic.com/paper/4mynt7shc6zk1",
  "venue": "Nature",
  "versions": []
}