PGC‐1α, a Novel Substrate for Protein Arginine Methyltransferase 7?

Abstract

Peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) is a protein that plays an important role in the regulation of energy metabolism. It participates in the regulation of both carbohydrate and lipid metabolism and is activated by insulin. For these reasons, it has been implicated in obesity, aging, diabetes and cardiomyopathy. Despite many studies on the role of this master regulator, the precise way it becomes regulated remains unknown. A recent study found that PGC‐1α becomes phosphorylated at Ser570 by kinase B (Akt/PKB) and this stops it from promoting gluconeogenesis and fatty acid oxidation. PGC‐1α is also modified by protein arginine methyltransferase 1 (PRMT1) at several arginine residues, which enhance its regulation. In this study, we set out to determine whether PGC‐1α is modified by PRMT7, another member of the PRMT family. We hypothesize that PRMT7 methylates PGC‐1α because it contains many RXR motifs, a known PRMT7 motif. In addition, they both are active at similar temperatures. To test this hypothesis, truncated constructs corresponding to PGC‐1α and full‐length PRMT7 were expressed and purified in bacterial cells. In vitro methylation reactions using tritiated AdoMet were carried out. Through fluorography of the methylation reactions, it was determined that PRMT7 methylates PGC‐1α within amino acid residues 532–640. Upon confirmation of the methylated arginine residue(s) through immunoblotting and mass spectrometry, further studies will be carried out to investigate the function of arginine methylation by PRMT7. These results will enhance our understanding of PGC‐1α with the broader goal of understanding its regulation in the context of obesity and diabetes.Support or Funding InformationCSULA Minority Access to Research Careers‐Undergraduate Student Training for Academic Research (MARC‐U*STAR), Grant: T34 GM008228 and Louis Stokes Alliance for Minority Participation (LSAMP), Grant: HRD‐1302873This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.