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Background <p>N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) is a prevalent and conserved RNA modification in eukaryotes. While its roles in the 3’ untranslated regions (3’ UTR) are well-studied, its role in the 5' UTR and its relationship with histone modifications remain underexplored.</p> Results <p>We demonstrate that m<sup>6</sup>A methylation in the 5’ UTR of mRNA triggers a downstream shift in H3K4me3 modification. This regulatory mechanism is conserved in <i>Arabidopsis</i>, rice, and chrysanthemum. The observed shift in H3K4me3 is genetically controlled by m<sup>6</sup>A modifiers and influences gene expression. MTA, the m<sup>6</sup>A methylase, preferentially binds to phosphorylated serine 5 (Ser5P)-CTD of RNA Pol II during transcription, leading to the displacement of ATX1, the H3K4me3 methylase. This dynamic binding of MTA and ATX1 to RNA Pol II ultimately results in the shift of H3K4me3 modification. Genetic evidence demonstrates that m<sup>6</sup>A in the 5' UTR controls H3K4me3 shift, thereby affecting <i>SEDOHEPTULOSE-BISPHOSPHATASE</i> expression and leaf senescence.</p> Conclusions <p>Our study provides new insights into the roles of m<sup>6</sup>A modification and its crosstalk with histone modification in 5’ UTRs, shedding light on the mechanism of m<sup>6</sup>A-mediated gene expression regulation.</p>

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mRNA m6A regulates gene expression via H3K4me3 shift in 5’ UTR

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月12日

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  • Yuna Yang,
  • Yuqing Huang,
  • Tian Wang,
  • Song Li,
  • Jiafu Jiang,
  • Sumei Chen,
  • Fadi Chen,
  • Likai Wang

摘要

Background

N6-methyladenosine (m6A) is a prevalent and conserved RNA modification in eukaryotes. While its roles in the 3’ untranslated regions (3’ UTR) are well-studied, its role in the 5' UTR and its relationship with histone modifications remain underexplored.

Results

We demonstrate that m6A methylation in the 5’ UTR of mRNA triggers a downstream shift in H3K4me3 modification. This regulatory mechanism is conserved in Arabidopsis, rice, and chrysanthemum. The observed shift in H3K4me3 is genetically controlled by m6A modifiers and influences gene expression. MTA, the m6A methylase, preferentially binds to phosphorylated serine 5 (Ser5P)-CTD of RNA Pol II during transcription, leading to the displacement of ATX1, the H3K4me3 methylase. This dynamic binding of MTA and ATX1 to RNA Pol II ultimately results in the shift of H3K4me3 modification. Genetic evidence demonstrates that m6A in the 5' UTR controls H3K4me3 shift, thereby affecting SEDOHEPTULOSE-BISPHOSPHATASE expression and leaf senescence.

Conclusions

Our study provides new insights into the roles of m6A modification and its crosstalk with histone modification in 5’ UTRs, shedding light on the mechanism of m6A-mediated gene expression regulation.