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

Protein arginine methyltransferases (PRMTs) catalyze the post-translational mono-methylation (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 similar to 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 IIPRMTs 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.

Automated summary

This study explores the cellular consequences of type I and II PRMTs through a variety of approaches, revealing their impact on cellular dimethylarginine levels, substrate recognition motifs, and phenotypic consequences. The research expands our understanding of PRMT substrate diversity, the arginine methylome, and the complex interplay between type I and II PRMTs.