{
  "abstract": "Background and Objectives: Spinocerebellar ataxia type 4 (SCA4) is caused by a GGC-repeat expansion in ZFHX3 encoding an expanded polyglycine tract causing p62- and ubiquitin-positive neuronal intranuclear inclusions (NIIs). In multiple polyglycine diseases NIIs sequester tRNA-splicing ligase complex (tRNA-LC) proteins, causing downstream functional defects linked to neurodegeneration. We assessed the localization of tRNA-LC proteins in SCA4 pontine neurons. Methods: Postmortem brain tissue from a genetically confirmed SCA4 patient was examined across multiple regions using immunofluorescence confocal microscopy for p62, ubiquitin and tRNA-LC proteins FAM98B, RTRAF, and RTCB. Results: In pontine neurons, FAM98B, RTRAF, and RTCB were incorporated into NII, accumulating in a distinct outer layer respective to a ubiquitin inner layer. This redistribution was accompanied by depletion of all three proteins from the soluble nucleoplasm. Discussion: Our findings link SCA4 to a tRNA-LC dysfunction phenotype shared by multiple GGC-repeat disorders, further supporting a unified pathological mechanism in polyglycine diseases.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "Mandi Gandelman",
      "orcid": "0000-0003-2697-0390"
    },
    {
      "name": "Karla P. Figueroa"
    },
    {
      "name": "Anton Classen"
    },
    {
      "name": "Daniel R. Scoles"
    },
    {
      "name": "Stefan M. Pulst"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0rpqwwp7sqdy9.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.26.761951",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761951v1.full",
  "id": "0rpqwwp7sqdy9",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761951v1",
  "language": "en",
  "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",
      "neuroscience"
    ],
    [
      "heading",
      "Article"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761951v1.full.pdf",
  "pmcid": "PMC13733956",
  "pmid": "42990418",
  "published": "2026-10-26",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/0rpqwwp7sqdy9.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:21:18Z",
      "native_id": "10.64898/2026.10.26.761951",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761951v1"
    },
    {
      "first_seen": "2026-11-08T12:23:37Z",
      "native_id": "PMC13733956",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.26.761951"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Accumulation of FAM98B and tRNA-Splicing Ligase Complex Proteins in Neuronal Intranuclear Inclusions in Spinocerebellar ataxia type 4.",
  "title_text": "Accumulation of FAM98B and tRNA-Splicing Ligase Complex Proteins in Neuronal Intranuclear Inclusions in Spinocerebellar ataxia type 4.",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:37Z",
  "url": "https://research.draconitic.com/paper/0rpqwwp7sqdy9",
  "venue": "bioRxiv",
  "versions": []
}