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

Xiaoqin Liu^1,2,3, Yilong Yao^1,2, Junyu Yan^1,2

¹Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-omics of MARA, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518124, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)

|August 31, 2025

Summary

Ribosomal protein S27-like (RPS27L) enhances skeletal muscle growth and regeneration. RPS27L, regulated by SIX4, promotes myoblast proliferation via liquid-liquid phase separation (LLPS) and IGF1 interaction.

Keywords:

IGF1 RPS27L liquid‐liquid phase separation muscle mass myofiber sizes skeletal muscle

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Published on: March 27, 2013

Area of Science:

Molecular Biology
Muscle Physiology

Background:

RNA-binding proteins (RBPs) are crucial for gene expression.
RPS27L's role in skeletal muscle development is largely unknown.

Purpose of the Study:

Investigate RPS27L functions in skeletal muscle.
Elucidate RPS27L's regulatory mechanisms in myogenesis.

Main Methods:

Utilized muscle-specific Rps27l knock-in (M-KI) mice.
Performed in vitro skeletal muscle cell studies.
Analyzed RPS27L regulation by SIX4 and interaction with IGF1.

Main Results:

M-KI mice showed increased muscle mass, myofiber size, and regeneration.
RPS27L overexpression boosted myoblast proliferation but inhibited differentiation.
SIX4 negatively regulates RPS27L expression.

Conclusions:

RPS27L plays a novel role in skeletal muscle development.
RPS27L-driven liquid-liquid phase separation (LLPS) is significant in myogenesis.
RPS27L interacts with IGF1 to regulate muscle growth.