title: Comparative Monomethylarginine Proteomics Suggests that Protein Arginine Methyltransferase 1 (PRMT1) is a Significant Contributor to Arginine Monomethylation inToxoplasma gondii.
abstract: Arginine methylation is a common posttranslational modification found on nuclear and cytoplasmic proteins that has roles in transcriptional regulation, RNA metabolism and DNA repair. The protozoan parasiteToxoplasma gondiihas a complex life cycle requiring transcriptional plasticity and has unique transcriptional regulatory pathways. Arginine methylation may play an important part in transcriptional regulation and splicing biology in this organism. TheT. gondiigenome contains five putative protein arginine methyltransferases (PRMTs), of which PRMT1 is important for cell division and growth. In order to better understand the function(s) of the posttranslational modification monomethyl arginine (MMA) inT. gondii, we performed a proteomic analysis of MMA proteins using affinity purification employing anti-MMA specific antibodies followed by mass spectrometry. The arginine monomethylome ofT. gondiicontains a large number of RNA binding proteins and multiple ApiAP2 transcription factors, suggesting a role for arginine methylation in RNA biology and transcriptional regulation. Surprisingly, 90% of proteins that are arginine monomethylated were detected as being phosphorylated in a previous phosphoproteomics study which raises the possibility of interplay between MMA and phosphorylation in this organism. Supporting this, a number of kinases are also arginine methylated. Because PRMT1 is thought to be a major PRMT inT. gondii, an organism which lacks a MMA-specific PRMT, we applied comparative proteomics to understand how PRMT1 might contribute to the MMA proteome inT. gondiiWe identified numerous putative PRMT1 substrates, which include RNA binding proteins, transcriptional regulators (e.g.AP2 transcription factors), and kinases. Together, these data highlight the importance of MMA and PRMT1 in arginine methylation inT. gondii, as a potential regulator of a large number of processes including RNA biology and transcription.
authors.affiliation: From the ‡Department of Pathology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Rama R
authors.initials: RR
authors.lastname: Yakubu
authors.affiliation: §Department of Medicine- Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Silmon de Monerri
authors.affiliation: ¶Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York.|‖Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Edward
authors.initials: E
authors.lastname: Nieves
authors.affiliation: From the ‡Department of Pathology, Albert Einstein College of Medicine, Bronx, New York; louis.weiss@einstein.yu.edu kami.kim@einstein.yu.edu.|§Department of Medicine- Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, New York.|**Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Kami
authors.initials: K
authors.lastname: Kim
authors.affiliation: From the ‡Department of Pathology, Albert Einstein College of Medicine, Bronx, New York; louis.weiss@einstein.yu.edu kami.kim@einstein.yu.edu.|§Department of Medicine- Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Louis M
authors.initials: LM
authors.lastname: Weiss
mesh_terms: D001120:Arginine / Q000032:analysis* / Q000737:chemistry; D002478:Cells, Cultured; D006801:Humans; D008745:Methylation; D010766:Phosphorylation; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015800:Protozoan Proteins / Q000378:metabolism; D013379:Substrate Specificity; D014122:Toxoplasma / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D001120:Arginine; D011484:Protein-Arginine N-Methyltransferases