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<p>Maintenance of the genome and epigenome stability is vital for animal longevity. Long noncoding RNAs, <i>roX</i>1 and <i>roX</i>2, are known to be important in the male X chromosome dosage complex in <i>Drosophila</i> males. However, their functions in <i>Drosophila</i> females have never been explored. This study demonstrates a role of <i>roX</i> RNAs in promoting heterochromatin formation in intestinal stem cells (ISCs) of <i>Drosophila</i> females under pathogen infection or aging. Increased heterochromatin formation in ISCs and progenitor enteroblasts (EBs) is associated with decreased active epigenetic modifications and global gene repression. Elevation of <i>roX</i> RNAs in ISCs promotes heterochromatinization and represses gene expression by recruiting heterochromatin proteins such as HP1a and Su(var)3-9. Overexpression of <i>roX</i> RNAs promotes ISCs hyperplasia, while their inactivation mitigates ISCs dysplasia and extends lifespan. Moreover, <i>Xist</i> RNA, the functional analog of <i>roX</i> RNAs, also promotes heterochromatin formation and ISCs hyperplasia in <i>Drosophila</i>, and significantly increases in aged people. Therefore, our findings reveal a role of <i>roX</i> RNAs in promoting heterochromatin expansion and controlling animal longevity.</p>

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roX1 and roX2 lncRNAs promote heterochromatinization in intestinal stem cells and impair longevity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月9日

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  • Kai-Le Li,
  • Chen Wang,
  • Yong-Hao Li,
  • Bo Peng,
  • Li Zheng,
  • Qinyun Che,
  • Xin-Yi Lu,
  • Donglin Li,
  • Yu-Tong Li,
  • Hui-Min Wei,
  • Jian-Feng Chang,
  • Wen-Fei Wang,
  • Mengmeng Liu,
  • Xiangnan Li,
  • Fangfang Jin,
  • Kai Liu,
  • Yabin Li,
  • Li-Wei Liu,
  • Mingyang Li,
  • Jian-Quan Ni,
  • Ting Xie,
  • Fang-Lin Sun

摘要

Maintenance of the genome and epigenome stability is vital for animal longevity. Long noncoding RNAs, roX1 and roX2, are known to be important in the male X chromosome dosage complex in Drosophila males. However, their functions in Drosophila females have never been explored. This study demonstrates a role of roX RNAs in promoting heterochromatin formation in intestinal stem cells (ISCs) of Drosophila females under pathogen infection or aging. Increased heterochromatin formation in ISCs and progenitor enteroblasts (EBs) is associated with decreased active epigenetic modifications and global gene repression. Elevation of roX RNAs in ISCs promotes heterochromatinization and represses gene expression by recruiting heterochromatin proteins such as HP1a and Su(var)3-9. Overexpression of roX RNAs promotes ISCs hyperplasia, while their inactivation mitigates ISCs dysplasia and extends lifespan. Moreover, Xist RNA, the functional analog of roX RNAs, also promotes heterochromatin formation and ISCs hyperplasia in Drosophila, and significantly increases in aged people. Therefore, our findings reveal a role of roX RNAs in promoting heterochromatin expansion and controlling animal longevity.