RPS27L Enhances Myogenesis and Muscle Mass by Targeting IGF1 Through Liquid-Liquid Phase Separation
文献类型： 外文期刊
作者： Liu, Xiaoqin 1 ; Yao, Yilong 1 ; Yan, Junyu 1 ; Zeng, Mu 1 ; Fan, Xinhao 1 ; Tang, Yijie 1 ; Li, Jiju 1 ; Liu, Yanwen 1 ; Yan, Shanying 1 ; Wang, Wei 1 ; Chen, Lijuan 1 ; Chen, Ruipu 1 ; Huang, Yuxin 1 ; Calnan, Honor 3 ; Wang, Heng 4 ; Gardner, Graham 3 ; Yang, Yalan 1 ; Tang, Zhonglin 1 ;
作者机构： 1.Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Key Lab Livestock & Poultry Multiom MARA, 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, Foshan 528226, Peoples R China
3.Murdoch Univ, Coll Environm & Life Sci, Murdoch, WA 6150, Australia
4.Shandong Agr Univ, Coll Anim Sci, Shandong Prov Key Lab Livestock Germplasm Innovat, Tai An 271000, Peoples R China
关键词： IGF1; liquid-liquid phase separation; muscle mass; myofiber sizes; RPS27L; skeletal muscle
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
页码：
收录情况： SCI
摘要： RNA-binding proteins (RBPs) play a pivotal role in post-transcriptional regulation of gene expression, critically influencing skeletal myogenesis, muscle growth, and regeneration. Despite the recent identification of RBP Rps27l (ribosomal protein S27-like) as a regulator affecting myogenic proliferation and differentiation, its functions and regulatory mechanisms in skeletal muscle development remain largely unknown. In this study, it is observed that muscle-specific Rps27l knock-in (M & horbar;KI) mice exhibit significantly increased muscle mass, enlarged myofiber size, a higher proportion of fast-twitch myofibers, and enhanced muscle regeneration capabilities compared to wild-type controls. Overexpression of Rps27l promotes myoblast proliferation while inhibiting differentiation in skeletal muscle cells. Mechanistically, it is revealed that the expression of Rps27l is negatively regulated by SIX4, a myogenic transcription factor. The N-terminal intrinsically disordered region of RPS27L facilitates liquid-liquid phase separation (LLPS) and interacts with IGF1 to collaboratively regulate myogenesis. The findings uncover the novel regulatory roles of RPS27L in skeletal muscle and highlight the significance of RPS27L-driven LLPS in myogenesis.
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