Scholarlink

<p>Understanding how chromosome 21 gene dosage contributes to neurodevelopmental phenotypes in trisomy 21 (T21) remains a fundamental challenge. Here, we perform transcriptome-wide RNA-sequencing of fetal cortical and hippocampal tissues from T21 cases and euploid controls collected during mid-gestation, a critical window for human brain development. We identify widespread gene expression dysregulation with significant enrichment for chromosome 21 genes and perturbation of neurodevelopmental, synaptic, and immune-related pathways. Among the most strongly dysregulated genes is <i>ADARB1</i>, a chromosome 21-encoded RNA editing enzyme, whose overexpression associates with increased adenosine-to-inosine RNA editing, with consistent over-editing at functionally important recoding sites in glutamate and GABA receptor-related genes, including <i>GRIK2</i>, <i>GRIA2</i>, <i>GRIA3</i>, and <i>GABRA3</i>, across cortex and hippocampus. Meta-analyses across independent transcriptomic datasets validate robust chromosome 21 dosage effects, including <i>ADARB1</i> overexpression and over-editing at 3′UTRs and <i>GRIA3</i>. These findings implicate dysregulated RNA editing as a post-transcriptional mechanism contributing to fetal neuropathology in T21.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Trisomy 21 Drives ADARB1 Overexpression and Premature RNA Recoding in the Developing Fetal Brain

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月31日

查看全文
  • Michael S. Breen,
  • Andy Yang,
  • Xuran Wang,
  • Miguel Rodriguez de los Santos,
  • Ran Tao,
  • Daniel R. Weinberger,
  • Joel E. Kleinman,
  • Kalina Mihova,
  • Gergana Stancheva,
  • Sylvia Savova,
  • Radka Kaneva,
  • Violeta Dimitrova,
  • Vladimir Vladimirov,
  • Thomas M. Hyde,
  • Joseph D. Buxbaum

摘要

Understanding how chromosome 21 gene dosage contributes to neurodevelopmental phenotypes in trisomy 21 (T21) remains a fundamental challenge. Here, we perform transcriptome-wide RNA-sequencing of fetal cortical and hippocampal tissues from T21 cases and euploid controls collected during mid-gestation, a critical window for human brain development. We identify widespread gene expression dysregulation with significant enrichment for chromosome 21 genes and perturbation of neurodevelopmental, synaptic, and immune-related pathways. Among the most strongly dysregulated genes is ADARB1, a chromosome 21-encoded RNA editing enzyme, whose overexpression associates with increased adenosine-to-inosine RNA editing, with consistent over-editing at functionally important recoding sites in glutamate and GABA receptor-related genes, including GRIK2, GRIA2, GRIA3, and GABRA3, across cortex and hippocampus. Meta-analyses across independent transcriptomic datasets validate robust chromosome 21 dosage effects, including ADARB1 overexpression and over-editing at 3′UTRs and GRIA3. These findings implicate dysregulated RNA editing as a post-transcriptional mechanism contributing to fetal neuropathology in T21.