{
  "abstract": "Pulmonary arterial hypertension (PAH) is associated with increased oxidative DNA damage, while haploinsufficiency of BMPR2 and other dosage-sensitive genes contributes directly to disease. Template-strand 8-oxoguanine (8-oxoG) provides a potential transient route to the same loss-of-function outcome through transcriptional mutagenesis without altering genomic DNA. RNA polymerase II can insert adenine opposite the lesion and generate a coding-sense C>A error in the nascent transcript. We asked whether this chemistry could generate premature-stop transcripts in dosage-sensitive PAH genes. Across 17,880 C>A-accessible coding positions in pulmonary vascular genes, 1,192 could generate premature termination codons, including 883 predicted to engage nonsense-mediated decay (NMD). Restricting these sites to expressed autosomal-dominant PAH genes with definitive ClinGen validity and established haploinsufficiency identified 116 NMD-prone positions in BMPR2, KDR, SMAD9, and TBX4. Eight exactly reproduce ClinVar pathogenic or likely pathogenic stop variants, including five in BMPR2. At BMPR2 c.1424, template-strand 8-oxoG and the expert-panel-reviewed genomic c.1424C>A allele is predicted to generate the same UAA-containing transcript. Published oxidized-guanine maps detect signal at seven of the eight coordinates, providing coordinate-level support for oxidative modification at these sites. These findings define a sequence-resolved route through which repairable oxidative DNA damage could transiently reproduce loss-of-function transcripts encoded by pathogenic PAH alleles without permanent genomic mutation.",
  "abstract_shown": true,
  "affiliations": [
    "Florida International University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "S. Moreno-Caceres"
    },
    {
      "name": "A. M. Hayes"
    },
    {
      "name": "A. Delmas Eliason"
    },
    {
      "affs": [
        0
      ],
      "name": "D. P. Marciano"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bdb4rkhhprd6s.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.01.756055",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.01.756055v1.full",
  "id": "bdb4rkhhprd6s",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.01.756055v1",
  "language": null,
  "licence": "PDM-1.0",
  "licence_label": "Public domain",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/publicdomain/mark/1.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioinformatics"
    ],
    [
      "openalex",
      "2740|Pulmonary Hypertension Research and Treatments"
    ]
  ],
  "openalex": "W7220960036",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.01.756055v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bdb4rkhhprd6s.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:40Z",
      "native_id": "10.64898/2026.10.01.756055",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.01.756055v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "8-Oxoguanine transcriptional miscoding can transiently reproduce PAH-associated premature-stop transcripts",
  "title_text": "8-Oxoguanine transcriptional miscoding can transiently reproduce PAH-associated premature-stop transcripts",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:40Z",
  "url": "https://research.draconitic.com/paper/bdb4rkhhprd6s",
  "venue": "bioRxiv",
  "versions": []
}