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<p><i>N</i><sup>6</sup>-methyladenosine (m<sup>6</sup>A) is a major RNA modification in the brain, regulating neural processes and contributing to disease mechanisms. Despite its importance, regional, age-specific and sex-specific m<sup>6</sup>A patterns in the human brain are still poorly described. Here, we profiled m<sup>6</sup>A mRNA modifications in five human brain regions (Brodmann areas 9 and 24, and the caudate, hippocampus and thalamus) across 25 individuals of different ages, ranging from 0 to 71 years old. We uncovered widespread regional differences for m<sup>6</sup>A patterns in the brain, notably in disease-risk genes, while age-related changes were most prominent in the prefrontal cortex. Integrating m<sup>6</sup>A data with whole-genome sequencing revealed that m<sup>6</sup>A modifications are associated with disease-related genetic loci. Our work identifies the spatial and temporal variation in m<sup>6</sup>A modifications and suggests how they could contribute to neurological disorders.</p>

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Multi-region m6A epitranscriptome profiling of the human brain reveals spatial and temporal variation and enrichment of disease-associated loci

  • 期刊论文

  • 发表日期：

    2025年12月9日

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  • Andrew M. Shafik,
  • Yong Peng,
  • Zijie Zhang,
  • Chen Chang,
  • Pingluan Wang,
  • Junghwa Lim,
  • Hongjun Song,
  • Chuan He,
  • Mengjie Chen,
  • Peng Jin

摘要

N6-methyladenosine (m6A) is a major RNA modification in the brain, regulating neural processes and contributing to disease mechanisms. Despite its importance, regional, age-specific and sex-specific m6A patterns in the human brain are still poorly described. Here, we profiled m6A mRNA modifications in five human brain regions (Brodmann areas 9 and 24, and the caudate, hippocampus and thalamus) across 25 individuals of different ages, ranging from 0 to 71 years old. We uncovered widespread regional differences for m6A patterns in the brain, notably in disease-risk genes, while age-related changes were most prominent in the prefrontal cortex. Integrating m6A data with whole-genome sequencing revealed that m6A modifications are associated with disease-related genetic loci. Our work identifies the spatial and temporal variation in m6A modifications and suggests how they could contribute to neurological disorders.