Inhibition of protein arginine methyltransferase 5 enhances hepatic mitochondrial biogenesis

The Journal of Biological Chemistry
Lei HuangQiong Wu

Abstract

Protein arginine methyltransferase 5 (PRMT5) regulates gene expression either transcriptionally by symmetric dimethylation of arginine residues on histones H4R3, H3R8, and H2AR3 or at the posttranslational level by methylation of nonhistone target proteins. Although emerging evidence suggests that PRMT5 functions as an oncogene, its role in metabolic diseases is not well-defined. We investigated the role of PRMT5 in promoting high-fat-induced hepatic steatosis. A high-fat diet up-regulated PRMT5 levels in the liver but not in other metabolically relevant tissues such as skeletal muscle or white and brown adipose tissue. This was associated with repression of master transcription regulators involved in mitochondrial biogenesis. In contrast, lentiviral short hairpin RNA-mediated reduction of PRMT5 significantly decreased phosphatidylinositol 3-kinase/AKT signaling in mouse AML12 liver cells. PRMT5 knockdown or knockout decreased basal AKT phosphorylation but boosted the expression of peroxisome proliferator-activated receptor α (PPARα) and PGC-1α with a concomitant increase in mitochondrial biogenesis. Moreover, by overexpressing an exogenous WT or enzyme-dead mutant PRMT5 or by inhibiting PRMT5 enzymatic activity with a small-mo...Continue Reading

References

Jan 18, 1994·Proceedings of the National Academy of Sciences of the United States of America·J C WuN Fausto
May 1, 1996·The Journal of Clinical Investigation·L C HudginsJ Hirsch
May 14, 1999·The Journal of Clinical Endocrinology and Metabolism·P MarceauJ G Kral
Oct 6, 1999·Obesity Research·N M Moussa, K J Claycombe
Mar 27, 2001·Current Opinion in Lipidology·G S Shelness, J A Sellers
Mar 1, 2002·British Journal of Cancer·G Pérez-TenorioUNKNOWN Southeast Sweden Breast Cancer Group
Mar 17, 2004·Cancer Treatment Reviews·Juan Angel Fresno VaraManuel González-Barón
Oct 27, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Odile DavidArnold R Brody
Oct 27, 2004·Apoptosis : an International Journal on Programmed Cell Death·M OsakiH Ito
Mar 3, 2005·The Journal of Clinical Endocrinology and Metabolism·Jukka WesterbackaHannele Yki-Järvinen
May 3, 2005·The Journal of Clinical Investigation·Kerry L DonnellyElizabeth J Parks
May 4, 2005·Molecular Cell·Mark T Bedford, Stéphane Richard
Dec 6, 2005·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Jian-Min TangXiu-Jun Chang
Dec 7, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Junji TsurutaniPhillip A Dennis
Aug 9, 2007·The American Journal of Clinical Nutrition·Angela M ZivkovicArun J Sanyal
Jan 20, 2009·Molecular Cell·Mark T Bedford, Steven G Clarke
Feb 27, 2009·Clinical Science·Christopher D ByrneMohamed H Ahmed
Jun 17, 2009·Nucleic Acids Research·A ScoumanneX Chen
Feb 2, 2010·Trends in Endocrinology and Metabolism : TEM·James R KrycerAndrew J Brown
Feb 20, 2010·Proceedings of the National Academy of Sciences of the United States of America·Mathieu Laplante, David M Sabatini
Feb 18, 2011·Cell Cycle·Ghada A Soliman
Dec 14, 2011·Trends in Endocrinology and Metabolism : TEM·Tae-Il Jeon, Timothy F Osborne
Sep 27, 2012·Cancer Discovery·Jason R Cantor, David M Sabatini
Mar 13, 2014·Current Pharmaceutical Design·Teresa Valero
Mar 13, 2014·Current Pharmaceutical Design·Fabian Sanchis-GomarFederico V Pallardó

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Citations

Oct 9, 2019·American Journal of Physiology. Endocrinology and Metabolism·Tiffany L vanLieshout, Vladimir Ljubicic
Jan 9, 2021·The Journal of Pathology. Clinical Research·Shuyu MeiTingguo Zhang
Feb 12, 2020·Genes & Diseases·Fen Zhu, Lixin Rui
Mar 21, 2021·Nature Reviews. Drug Discovery·Qin WuDalia Barsyte-Lovejoy
Apr 9, 2021·Cell Transplantation·Jianhao HuangHan Lei
May 8, 2020·Current Protein & Peptide Science·Ayad A Al-HamashiRong Huang
Aug 9, 2021·Translational Oncology·Yu LeiDean Tian
May 29, 2020·Journal of the American Society for Mass Spectrometry·Niveda SundararamanVidya Venkatraman
Sep 14, 2021·Frontiers in Cell and Developmental Biology·Zhenzhen LiangXiaodong Liu

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