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  • PRMT5 mediates FoxO1 methylation and subcellular localization to regulate lipophagy in myogenic progenitors.

PRMT5 mediates FoxO1 methylation and subcellular localization to regulate lipophagy in myogenic progenitors.

Cell reports (2023-10-26)
Kun Ho Kim, Stephanie N Oprescu, Madigan M Snyder, Aran Kim, Zhihao Jia, Feng Yue, Shihuan Kuang
ABSTRACT

Development is regulated by various factors, including protein methylation status. While PRMT5 is well known for its roles in oncogenesis by mediating symmetric di-methylation of arginine, its role in normal development remains elusive. Using Myod1Cre to drive Prmt5 knockout in embryonic myoblasts (Prmt5MKO), we dissected the role of PRMT5 in myogenesis. The Prmt5MKO mice are born normally but exhibit progressive muscle atrophy and premature death. Prmt5MKO inhibits proliferation and promotes premature differentiation of embryonic myoblasts, reducing the number and regenerative function of satellite cells in postnatal mice. Mechanistically, PRMT5 methylates and destabilizes FoxO1. Prmt5MKO increases the total FoxO1 level and promotes its cytoplasmic accumulation, leading to activation of autophagy and depletion of lipid droplets (LDs). Systemic inhibition of autophagy in Prmt5MKO mice restores LDs in myoblasts and moderately improves muscle regeneration. Together, PRMT5 is essential for muscle development and regeneration at least partially through mediating FoxO1 methylation and LD turnover.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Laminin antibody produced in rabbit, 0.5 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Monoclonal ANTI-FLAG® M2 antibody produced in mouse, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)
Sigma-Aldrich
Anti-dimethyl-Arginine Antibody, symmetric (SYM10), serum, Upstate®
Sigma-Aldrich
4-Hydroxytamoxifen, ≥70% Z isomer (remainder primarily E-isomer)
Sigma-Aldrich
Phenylmethyl Sulfonyl Fluoride, OmniPur® Grade, >=99.0%