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<p>Divergent transcription from bidirectional promoters is frequently observed in eukaryotic genomes, but the biological relevance of divergent RNA transcripts (DT) is unknown. We identified and characterized <i>BDNF-DT</i>, a novel DT gene, and <i>BDNF-AS-DT</i>, a novel readthrough gene, in the locus containing <i>BDNF</i>, a gene with key roles in neuronal development, differentiation, and synaptic plasticity. <i>BDNF-DT</i> is independent from the known <i>BDNF</i> antisense (<i>BDNF-AS</i>), and its expression is developmentally regulated and positively correlated with <i>BDNF</i> in human postmortem dorsolateral prefrontal cortex (DLPFC). <i>BDNF-DT</i> and <i>BDNF-AS-DT</i> expression increase after induced depolarization, but the temporal dynamics follow expression of <i>BDNF</i>, suggesting a regulatory role. Moreover, CRISPR-mediated upregulation of <i>BDNF</i> in human neural progenitor cells drives <i>BDNF-DT</i> expression. Finally, <i>BDNF-DT</i> shows higher expression in DLPFC from patients diagnosed with schizophrenia compared to neurotypical controls, and genetically predicted lower expression of the <i>BDNF-AS-DT</i> readthrough transcript is associated with schizophrenia and with the schizophrenia-associated C allele of the rs6265 single-nucleotide polymorphism. These findings identify <i>BDNF-DT</i> and <i>BDNF-AS-DT</i> as novel, low-abundance genes that show coordinated expression with <i>BDNF</i> and association with schizophrenia risk, though their biological significance requires further validation given detection limitations and the need to establish causal roles.</p>

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BDNF-DT and BDNF-AS-DT: novel genes in the BDNF locus

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月30日

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  • Svitlana V. Bach,
  • Giovanna Punzi,
  • Nuri E. Smith,
  • Sreya Mukherjee,
  • Joo Heon Shin,
  • Qiang Chen,
  • Geo Pertea,
  • Leonardo Collado-Torres,
  • Kristen R. Maynard,
  • Stephanie C. Page,
  • Joel E. Kleinman,
  • Thomas M. Hyde,
  • Daniel R. Weinberger,
  • Keri Martinowich,
  • Gianluca Ursini

摘要

Divergent transcription from bidirectional promoters is frequently observed in eukaryotic genomes, but the biological relevance of divergent RNA transcripts (DT) is unknown. We identified and characterized BDNF-DT, a novel DT gene, and BDNF-AS-DT, a novel readthrough gene, in the locus containing BDNF, a gene with key roles in neuronal development, differentiation, and synaptic plasticity. BDNF-DT is independent from the known BDNF antisense (BDNF-AS), and its expression is developmentally regulated and positively correlated with BDNF in human postmortem dorsolateral prefrontal cortex (DLPFC). BDNF-DT and BDNF-AS-DT expression increase after induced depolarization, but the temporal dynamics follow expression of BDNF, suggesting a regulatory role. Moreover, CRISPR-mediated upregulation of BDNF in human neural progenitor cells drives BDNF-DT expression. Finally, BDNF-DT shows higher expression in DLPFC from patients diagnosed with schizophrenia compared to neurotypical controls, and genetically predicted lower expression of the BDNF-AS-DT readthrough transcript is associated with schizophrenia and with the schizophrenia-associated C allele of the rs6265 single-nucleotide polymorphism. These findings identify BDNF-DT and BDNF-AS-DT as novel, low-abundance genes that show coordinated expression with BDNF and association with schizophrenia risk, though their biological significance requires further validation given detection limitations and the need to establish causal roles.