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LncRNA-MEG3 Regulates Muscle Mass and Metabolic Homeostasis by Facilitating SUZ12 Liquid-Liquid Phase Separation

文献类型： 外文期刊

作者： Yao, Yilong 1 ; Yan, Chao 1 ; Huang, Haibo 1 ; Wang, Shilong 1 ; Li, Jiaying 4 ; Chen, Yun 1 ; Qu, Xiaolu 5 ; Bao, Qi 1 ; Xu, Lingna 1 ; Zhang, Yuanyuan 1 ; Fan, Danyang 5 ; He, Xia 7 ; Liu, Yanwen 5 ; Zhang, Yongsheng 1 ; Yang, Yalan 1 ; Tang, Zhonglin 1 ;

作者机构： 1.Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Shenzhen Branch, Guangdong Lab Lingnan Modern Agr,Key Lab Livestock, Shenzhen 518124, Peoples R China

2.Chinese Acad Agr Sci, Kunpeng Inst Modern Agr Foshan, Foshan 528226, Peoples R China

3.Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Key Lab Livestock & Poultry Multi Om MARA, Shenzhen 518124, Peoples R China

4.Capital Med Univ, Beijing Tongren Hosp, Beijing 100730, Peoples R China

5.Huazhong Agr Univ, Key Lab Agr Anim Genet Breeding & Reprod, Minist Educ, Wuhan 430070, Peoples R China

6.Huazhong Agr Univ, Key Lab Swine Genet & Breeding, Minist Agr & Rural Affairs, Wuhan 430070, Peoples R China

7.Foshan Univ, Sch Anim Sci & Technol, Foshan 528225, Peoples R China

关键词： fat infiltration; lncRNA-MEG3; muscle atrophy; oxidative muscle fibers; SUZ12 LLPS

期刊名称：ADVANCED SCIENCE （ 影响因子：14.1； 五年影响因子：15.6 ）

ISSN：

年卷期： 2025 年 12 卷 23 期

页码：

收录情况： SCI

摘要： Skeletal muscle plays a crucial role in maintaining motor function and metabolic homeostasis, with its loss or atrophy leading to significant health consequences. Long non-coding RNAs (lncRNAs) have emerged as key regulators in muscle biology; however, their precise roles in muscle function and pathology remain to be fully elucidated. This study demonstrates that lncRNA maternally expressed gene 3 (MEG3) is preferentially expressed in slow-twitch muscle fibers and dynamically regulated during muscle development, aging, and in the context of Duchenne muscular dystrophy (DMD). Using both loss- and gain-of-function mice models, this study shows that lncRNA-MEG3 is critical for preserving muscle mass and function. Its depletion leads to muscle atrophy, mitochondrial dysfunction, and impaired regenerative capacity, while overexpression enhances muscle mass, increases oxidative muscle fiber content, and improves endurance. Notably, lncRNA-MEG3 overexpression in MDX mice significantly alleviates muscle wasting and adipose tissue infiltration. Mechanistically, this study uncovers a novel interaction between lncRNA-MEG3 and the polycomb repressive complex 2 (PRC2), where lncRNA-MEG3 binds to SUZ12 polycomb repressive complex 2 subunit (Suz12), stabilizes PRC2, facilitates SUZ12 liquid-liquid phase separation (LLPS), and regulates the epigenetic modulation of four and a half lim domains 3 (Fhl3) and ring finger protein 128 (Rnf128). These findings not only highlight the crucial role of lncRNA-MEG3 in muscle homeostasis but also provide new insights into lncRNA-based therapeutic strategies for muscle-related diseases.

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