RPS27L Enhances Myogenesis and Muscle Mass by Targeting IGF1 Through Liquid-Liquid Phase Separation

文献类型： 外文期刊

第一作者： Liu, Xiaoqin

作者： Liu, Xiaoqin;Yao, Yilong;Yan, Junyu;Zeng, Mu;Fan, Xinhao;Tang, Yijie;Li, Jiju;Liu, Yanwen;Yan, Shanying;Wang, Wei;Chen, Lijuan;Chen, Ruipu;Huang, Yuxin;Yang, Yalan;Tang, Zhonglin;Liu, Xiaoqin;Yao, Yilong;Yan, Junyu;Zeng, Mu;Fan, Xinhao;Tang, Yijie;Li, Jiju;Liu, Yanwen;Yan, Shanying;Wang, Wei;Chen, Lijuan;Chen, Ruipu;Huang, Yuxin;Yang, Yalan;Tang, Zhonglin;Liu, Xiaoqin;Calnan, Honor;Gardner, Graham;Wang, Heng

作者机构：

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

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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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