@article{285e4b6aacd444f48833f5e78596f032,
title = "Independent transcriptomic and proteomic regulation by type I and II protein arginine methyltransferases",
abstract = "Protein arginine methyltransferases (PRMTs) catalyze the post-translational monomethylation (Rme1), asymmetric (Rme2a), or symmetric (Rme2s) dimethylation of arginine. To determine the cellular consequences of type I (Rme2a) and II (Rme2s) PRMTs, we developed and integrated multiple approaches. First, we determined total cellular dimethylarginine levels, revealing that Rme2s was ∼3% of total Rme2 and that this percentage was dependent upon cell type and PRMT inhibition status. Second, we quantitatively characterized in vitro substrates of the major enzymes and expanded upon PRMT substrate recognition motifs. We also compiled our data with publicly available methylarginine-modified residues into a comprehensive database. Third, we inhibited type I and II PRMTs and performed proteomic and transcriptomic analyses to reveal their phenotypic consequences. These experiments revealed both overlapping and independent PRMT substrates and cellular functions. Overall, this study expands upon PRMT substrate diversity, the arginine methylome, and the complex interplay of type I and II PRMTs.",
keywords = "cell biology, molecular biology",
author = "Maron, {Maxim I.} and Lehman, {Stephanie M.} and Sitaram Gayatri and DeAngelo, {Joseph D.} and Subray Hegde and Lorton, {Benjamin M.} and Yan Sun and Bai, {Dina L.} and Simone Sidoli and Varun Gupta and Marunde, {Matthew R.} and Bone, {James R.} and Sun, {Zu Wen} and Bedford, {Mark T.} and Jeffrey Shabanowitz and Hongshan Chen and Hunt, {Donald F.} and David Shechter",
note = "Funding Information: This work was supported by the National Institutes of Health : R01GM108646 to D.S., R01GM037537 to D.F.H, R01GM126421 to M.T.B., and R44GM112234 to Z.W.S. D.S. was also supported by the American Lung Association Discovery Award LCD-564723 and an Irma T. Hirschl Career Scientist Award. S.S. gratefully acknowledges the Leukemia Research Foundation (Hollis Brownstein New Investigator Research Grant), AFAR (Sagol Network GerOmic Award), the Einstein Nathan Shock Center for the Biology of Aging, Relay Therapeutics, Deerfield (Xseed award), and the NIH P30 grant CA013330 47 . Thank you to Benjamin A. Garcia for sharing resources and instruments. Thank you to Anne R. Bresnick for her help with microscopy. Thank you to Protein Metrics for generously providing the Byonic search algorithm which was used in this work. We thank Emmanuel S. Burgos for purified PRMT1 and PRMT5 proteins. We appreciate early access to PRMT inhibitors from the Structural Genomics Consortium (Toronto). Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = sep,
day = "24",
doi = "10.1016/j.isci.2021.102971",
language = "English (US)",
volume = "24",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "9",
}