roX1 and roX2 lncRNAs promote heterochromatinization in intestinal stem cells and impair longevity
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.
Authors
- Qinyun Che
- Jian-Feng Chang
- Kai-Le Li
- Xinyi Lu (ORCID: https://orcid.org/0000-0001-5961-6625)
- Yutong Li (ORCID: https://orcid.org/0000-0001-8653-6698)
- Wenfei Wang (ORCID: https://orcid.org/0000-0003-3360-8082)
- Yabin Li (ORCID: https://orcid.org/0000-0002-0540-128X)
- Hui-Min Wei
- Li Zheng (ORCID: https://orcid.org/0009-0005-3234-665X)
- Chen Wang (ORCID: https://orcid.org/0009-0001-0301-3179)
- Li-Wei Liu
- Donglin Li
- Xiangnan Li
- Jian-Quan Ni (ORCID: https://orcid.org/0000-0001-9332-8440)
- Fangfang Jin
- Mengmeng Liu (ORCID: https://orcid.org/0009-0006-9644-5099)
- Bo Peng (ORCID: https://orcid.org/0000-0002-3983-4390)
- Mingyang Li
- Ting Xie (ORCID: https://orcid.org/0000-0003-4769-986X)
- Kai Liu (ORCID: https://orcid.org/0000-0003-1060-8119)
- Fang-Lin Sun (ORCID: https://orcid.org/0000-0003-1174-6468)
- Yong-Hao Li
Institutions
- Tulane University (US)
- Tongji University (CN)
- Hong Kong University of Science and Technology (HK)
- Chinese PLA General Hospital (CN)
- Beijing National Laboratory for Molecular Sciences (CN)
- Hangzhou DAC Biotech (China) (CN)
- First Affiliated Hospital of Zhengzhou University (CN)
- State Key Laboratory of Molecular Oncology
- University of Hong Kong (HK)
- Tsinghua University (CN)
Publication Details
- Journal
- EMBO Reports
- Published
- 2026-05-09
- DOI
- https://doi.org/10.1038/s44319-026-00791-8
- Primary Topic
- Chromosomal and Genetic Variations
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Ministry of Science and Technology of the People's Republic of China
- Dream Project of Ministry of Science and Technology of the People's Republic of China