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

Autor:	Kim KH; Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA., Oprescu SN; Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA; Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA., Snyder MM; Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA; Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA., Kim A; Department of Pharmacy, Purdue University, West Lafayette, IN 47907, USA., Jia Z; Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA., Yue F; Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA., Kuang S; Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA; Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA. Electronic address: skuang@purdue.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Nov 28; Vol. 42 (11), pp. 113329. Date of Electronic Publication: 2023 Oct 25.
DOI:	10.1016/j.celrep.2023.113329
Abstrakt:	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 Myod1 Cre to drive Prmt5 knockout in embryonic myoblasts (Prmt5 MKO ), we dissected the role of PRMT5 in myogenesis. The Prmt5 MKO mice are born normally but exhibit progressive muscle atrophy and premature death. Prmt5 MKO 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. Prmt5 MKO 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 Prmt5 MKO 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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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