Phase separation of MRG15 delays cellular senescence.

Yuwen Li, Xinrong Jin, Chunyu Yu, Min Zuo, Liquan Hong, Mingwei Wang, Chenyan Zhao, Aiwei Wu, Jianjun Wang, Zhenyu Ju, Hu Wang

Zhejiang Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, The Third People's Hospital of Deqing, Department of Cardiology, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China.Zhejiang Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, The Third People's Hospital of Deqing, Department of Cardiology, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China. · pubmed

Paper

Abstract

Phase separation, a biophysical process that segregates subcellular environments into condensates, has been recognized for its role in transcriptional regulation. However, the extent of its influence on cellular senescence processes remains to be fully elucidated. We established that MRG15 depletion leads to cellular senescence in human mesenchymal stem cells (hMSCs). MRG15 can form phase-separated liquid condensates via its intrinsically disordered region (IDR). IDR deletion and replacement assays revealed that MRG15 condensation is crucial to hMSC senescence. According to the epigenomic and transcriptomic analysis, MRG15 depletion impacts pathways integral to the cell cycle and the senescence process, as evidenced by the diminished binding and the modified expression of key genes, including p53, CDKN1A, LMNB1, CCNB1, NPM1, MYC, and HMGB2. Our findings establish a link between phase separation and senescence regulation and present a promising new therapeutic target for the alleviation of age-related diseases and the potential extension of lifespan.

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Research summary

MRG15 phase separation is crucial for regulating cellular senescence in human mesenchymal stem cells. The study addresses a mechanism related to cellular aging, linking phase separation to the senescence process, which is relevant for understanding and potentially mitigating age-related diseases.

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