PRMT5 links lipid metabolism to contractile function of skeletal muscles.

Autor: Kim KH; Department of Animal Sciences, Purdue University, West Lafayette, IN, USA., Jia Z; Department of Animal Sciences, Purdue University, West Lafayette, IN, USA., Snyder M; Department of Animal Sciences, Purdue University, West Lafayette, IN, USA.; Department of Biological Sciences, Purdue University, West Lafayette, IN, USA., Chen J; Department of Animal Sciences, Purdue University, West Lafayette, IN, USA., Qiu J; Department of Animal Sciences, Purdue University, West Lafayette, IN, USA., Oprescu SN; Department of Animal Sciences, Purdue University, West Lafayette, IN, USA.; Department of Biological Sciences, Purdue University, West Lafayette, IN, USA., Chen X; Department of Animal Sciences, Purdue University, West Lafayette, IN, USA., Syed SA; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA., Yue F; Department of Animal Sciences, Purdue University, West Lafayette, IN, USA., Roseguini BT; Department of Health and Kinesiology, Purdue University, West Lafayette, IN, USA., Imbalzano AN; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA., Hu C; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, USA.; Center for Cancer Research, Purdue University, West Lafayette, IN, USA., Kuang S; Department of Animal Sciences, Purdue University, West Lafayette, IN, USA.; Center for Cancer Research, Purdue University, West Lafayette, IN, USA.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2023 Aug 03; Vol. 24 (8), pp. e57306. Date of Electronic Publication: 2023 Jun 19.
DOI: 10.15252/embr.202357306
Abstrakt: Skeletal muscle plays a key role in systemic energy homeostasis besides its contractile function, but what links these functions is poorly defined. Protein Arginine Methyl Transferase 5 (PRMT5) is a well-known oncoprotein but also expressed in healthy tissues with unclear physiological functions. As adult muscles express high levels of Prmt5, we generated skeletal muscle-specific Prmt5 knockout (Prmt5 MKO ) mice. We observe reduced muscle mass, oxidative capacity, force production, and exercise performance in Prmt5 MKO mice. The motor deficiency is associated with scarce lipid droplets in myofibers due to defects in lipid biosynthesis and accelerated degradation. Specifically, PRMT5 deletion reduces dimethylation and stability of Sterol Regulatory Element-Binding Transcription Factor 1a (SREBP1a), a master regulator of de novo lipogenesis. Moreover, Prmt5 MKO impairs the repressive H4R3 symmetric dimethylation at the Pnpla2 promoter, elevating the level of its encoded protein ATGL, the rate-limiting enzyme catalyzing lipolysis. Accordingly, skeletal muscle-specific double knockout of Pnpla2 and Prmt5 normalizes muscle mass and function. Together, our findings delineate a physiological function of PRMT5 in linking lipid metabolism to contractile function of myofibers.
(© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
Databáze: MEDLINE
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