文章基本信息

标题：Independent transcriptomic and proteomic regulation by type I and II protein arginine methyltransferases
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作者：Maxim I. Maron ; Stephanie M. Lehman ; Sitaram Gayatri 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：9
页码：1-31
DOI：10.1016/j.isci.2021.102971
语种：English
出版社：Elsevier
摘要：SummaryProtein 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 characterizedin vitrosubstrates 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.Graphical abstractDisplay OmittedHighlights•Rapid and sensitive direct-injection MS/MS dimethylarginine quantification•Quantitative methyltransferase assays on oriented peptide array libraries (OPALs)•PTMScan, proteomic, transcriptomic, and phenotypic analysis of PRMT inhibition•Compilation of our data and publicly available arginine methylome dataMolecular biology; Cell biology