Independent transcriptomic and proteomic regulation by type I and II protein arginine methyltransferases

Maxim I. Maron, Stephanie M. Lehman, Sitaram Gayatri, Joseph D. DeAngelo, Subray Hegde, Benjamin M. Lorton, Yan Sun, Dina L. Bai, Simone Sidoli, Varun Gupta, Matthew R. Marunde, James R. Bone, Zu Wen Sun, Mark T. Bedford, Jeffrey Shabanowitz, Hongshan Chen, Donald F. Hunt, David Shechter

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number102971
JournaliScience
Volume24
Issue number9
DOIs
StatePublished - Sep 24 2021
Externally publishedYes

Keywords

  • cell biology
  • molecular biology

ASJC Scopus subject areas

  • General

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