{
  "abstract": "Autism spectrum disorder has been linked to disrupted RNA processing during corticogenesis, yet variant-specific mechanisms remain difficult to resolve. Isogenic cerebral organoids derived from a patient-derived induced pluripotent stem cell (iPSC) line carrying the HNRNPH2-R114W variant and its CRISPR-corrected counterpart serve as a human developmental model to investigate variant-associated RNA dysregulation. Imaging quantification and exploratory bulk RNA sequencing, performed at a single developmental time point on a pooled organoid RNA from each genotype, identify coordinated remodeling of neuronal and metabolic programs, along with junction-centered splicing dysregulation involving 6,310 differentially used junctions. Computational structural docking situates HNRNPH2 RNA recognition motifs (RRMs) 1–3 within a spliceosomal context and locates residue R114 near a predicted RNA-contact interface, indicating that the R114W substitution may alter RNA engagement. Integration of differential expression with event- and isoform-level analyses identifies regulatory hubs enriched for axon guidance and synaptic signaling pathways. Single-cell-reference-based deconvolution suggests modest compositional shifts that are unlikely to account for the extent of transcriptional and splicing alterations observed. Collectively, these findings imply HNRNPH2-R114W in widespread RNA rewiring and define candidate isoform-level endpoints for mechanistic and therapeutic investigation in human cortical organoids. These molecular signatures open new avenues to examine how HNRNPH2-associated RNA dysregulation evolves across developmental time and recurs across independent biological contexts, providing a foundation for further mechanistic studies of this rare neurodevelopmental disorder.",
  "abstract_shown": true,
  "affiliations": [
    "Dell Pediatric Research Institute, University of Texas at Austin , , ,",
    "To Cure a Rose Foundation, Austin Community College , , ,",
    "Computational Systems Biology Laboratory, Universidade de São Paulo , ,",
    "Baylor College of Medicine, Center for Precision Environmental Health , , ,",
    "AlphaRose Therapeutics , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Carlo Donato Caiaffa"
    },
    {
      "affs": [
        1
      ],
      "name": "Neda Ghousifam"
    },
    {
      "affs": [
        2
      ],
      "name": "Stephan Lloyd Watkins"
    },
    {
      "affs": [
        2
      ],
      "name": "Helder I. Nakaya"
    },
    {
      "affs": [
        1
      ],
      "name": "Rodney A. Bowling"
    },
    {
      "affs": [
        3
      ],
      "name": "Richard H. Finnell"
    },
    {
      "affs": [
        4
      ],
      "name": "Robert M. Cabrera"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/db251tjax32r2.bib",
  "cited_by": 0,
  "doi": "10.3389/fbioe.2026.1922305",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13719587/?tool=EBI",
  "id": "db251tjax32r2",
  "issns": [
    "2296-4185"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13719587",
  "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": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "1312|RNA Research and Splicing"
    ]
  ],
  "openalex": "W7222478678",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13719587/pdf/?tool=EBI",
  "pmcid": "PMC13719587",
  "pmid": "42964376",
  "published": "2026-10-16",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/db251tjax32r2.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:36Z",
      "native_id": "PMC:PMC13719587",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13719587"
    },
    {
      "first_seen": "2026-11-02T12:23:31Z",
      "native_id": "PMC13719587",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fbioe.2026.1922305"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|RNA Research and Splicing",
      "subfield": "molecular-biology"
    }
  ],
  "title": "HNRNPH2-R114W remodels RNA splicing and neurodevelopmental gene programs in isogenic cerebral organoids",
  "title_text": "HNRNPH2-R114W remodels RNA splicing and neurodevelopmental gene programs in isogenic cerebral organoids",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:20:37Z",
  "url": "https://research.draconitic.com/paper/db251tjax32r2",
  "venue": "Frontiers in bioengineering and biotechnology",
  "versions": []
}