{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:37:46Z","timestamp":1790807866670,"version":"4.1.0"},"reference-count":45,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,6,1]]},"abstract":"<jats:p>CARM1 (co-activator-associated arginine methyltransferase 1)\/PRMT4 (protein arginine methyltransferase 4), functions as a co-activator for transcription factors that are regulators of muscle fibre type and oxidative metabolism, including PGC (peroxisome-proliferator-activated receptor \u03b3 co-activator)-1\u03b1 and MEF2 (myocyte enhancer factor 2). We observed significantly higher Prmt4 mRNA expression in comparison with Prmt1\u2013Prmt6 mRNA expression in mouse muscle (in vitro and in vivo). Transfection of Prmt4 siRNA (small interfering RNA) into mouse skeletal muscle C2C12 cells attenuated PRMT4 mRNA and protein expression. We subsequently performed additional qPCR (quantitative PCR) analysis (in the context of metabolism) to examine the effect of Prmt4 siRNA expression on &amp;gt;200 critical genes that control (and are involved in) lipid, glucose and energy homoeostasis, and circadian rhythm. This analysis revealed a strikingly specific metabolic expression footprint, and revealed that PRMT4 is necessary for the expression of genes involved in glycogen metabolism in skeletal muscle cells. Prmt4 siRNA expression selectively suppressed the mRNAs encoding Gys1 (glycogen synthase 1), Pgam2 (muscle phosphoglycerate mutase 2) and Pygm (muscle glycogen phosphorylase). Significantly, PGAM, PYGM and GYS1 deficiency in humans causes glycogen storage diseases type\u00a0X, type\u00a0V\/McArdle's disease and type\u00a00 respectively. Attenuation of PRMT4 was also associated with decreased expression of the mRNAs encoding AMPK (AMP-activated protein kinase) \u03b12\/\u03b33 (Prkaa2 and Prkag3) and p38 MAPK (mitogen-activated protein kinase), previously implicated in Wolff\u2013Parkinson\u2013White syndrome and Pompe Disease (glycogen storage disease type\u00a0II). Furthermore, stable transfection of two PRMT4-site-specific (methyltransferase deficient) mutants (CARM1\/PRMT4 VLD and CARM1E267Q) significantly repressed the expression of Gys1, Pgam2 and AMPK\u03b33. Finally, in concordance, we observed increased and decreased glycogen levels in PRMT4 (native)- and VLD (methylation deficient mutant)-transfected skeletal muscle cells respectively. This demonstrated that PRMT4 expression and the associated methyltransferase activity is necessary for the gene expression programme involved in glycogen metabolism and human glycogen storage diseases.<\/jats:p>","DOI":"10.1042\/bj20112033","type":"journal-article","created":{"date-parts":[[2012,3,20]],"date-time":"2012-03-20T09:17:07Z","timestamp":1332235027000},"page":"323-331","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["CARM1\/PRMT4 is necessary for the glycogen gene expression programme in skeletal muscle cells"],"prefix":"10.1042","volume":"444","author":[{"given":"Shu-Ching\u00a0Mary","family":"Wang","sequence":"first","affiliation":[{"name":"Obesity Research Centre, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis\u00a0H.","family":"Dowhan","sequence":"additional","affiliation":[{"name":"Obesity Research Centre, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie\u00a0A.","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Obesity Research Centre, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George\u00a0E.\u00a0O.","family":"Muscat","sequence":"additional","affiliation":[{"name":"Obesity Research Centre, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2012,5,11]]},"reference":[{"key":"2021112217321821000_B1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/0006-291X(67)90533-5","article-title":"Enzymatic methylation of protein fractions from calf thymus nuclei","volume":"29","author":"Paik","year":"1967","journal-title":"Biochem. 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