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LncRNA RMG controls liquid-liquid phase separation of MEIS2 to regulate myogenesis

文献类型： 外文期刊

作者： Yao, Yilong 1 ; Zhou, Rong 4 ; Yan, Chao 1 ; Yan, Shanying 1 ; Han, Guohao 1 ; Liu, Yanwen 2 ; Fan, Danyang 2 ; Chen, Zhilong 1 ; Fan, Xinhao 2 ; Chen, Yun 2 ; Li, Jiaying 6 ; 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, Shenzhen 518124, Peoples R China

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

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

4.Chinese Acad Agr Sci, Inst Anim Sci, Beijing 100193, Peoples R China

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

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

关键词： Lnc-RMG; Myogenesis; MEIS2 LLPS

期刊名称：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES （ 影响因子：8.5； 五年影响因子：8.7 ）

ISSN： 0141-8130

年卷期： 2025 年 310 卷

页码：

收录情况： SCI

摘要： Long non-coding RNAs (lncRNAs) regulate liquid-liquid phase separation (LLPS), driving the formation of biomolecular condensates essential for cellular function. However, this regulatory mechanism is yet to be reported in skeletal muscles. In this study, we comprehensively analyzed lncRNAs in skeletal muscle across multiple pig breeds, developmental stages, and tissues. Our analysis identified over 10,000 novel lncRNAs. We found that the lnc-regulator of muscle growth (lnc-RMG) regulates myogenesis by modulating the LLPS of Meis homeobox 2 (MEIS2). Lnc-RMG was specifically expressed in the skeletal muscle, with significantly higher expression in the fetal stage than in the embryonic stage. Notably, lnc-RMG was highly conserved between pigs and humans and exhibits similar biological functions in myogenesis. Furthermore, lnc-RMG knockdown promoted skeletal muscle regeneration. Mechanistically, lnc-RMG produces mature microRNA (miR)-133a-3p, which targets and inhibits MEIS2 expression, thereby inhibiting MEIS2 LLPS. This inhibition promoted the transcription of transforming growth factor-beta receptor II (TGF beta R2), ultimately regulating myogenesis. Overall, our findings revealed a novel lnc-RMG/miR-133a-3p/MEIS2/TGF beta R2 axis that regulated myogenesis through LLPS and provided new insights into the molecular mechanisms that drive muscle development and regeneration. These findings highlight potential therapeutic targets for muscle-related diseases and novel strategies for livestock improvement.

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