Protein arginine methylation: Cellular functions and methods of analysis
ABSTRACT During the last few years, new members of the growing family of protein arginine methyltransferases (PRMTs) have been identified and the role of arginine methylation in manifold cellular processes like signaling, RNA processing, transcription, and subcellular transport has been extensively investigated. In this review, we describe recent methods and findings that have yielded new insights into the cellular functions of arginine-methylated proteins, and we evaluate the currently used procedures for the detection and analysis of arginine methylation.
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- "Thus, RNA-binding proteins are key regulators of parasite function. RNA-binding proteins constitute a large number of arginine methylated proteins in higher organisms (Pahlich et al. 2006; Bedford and Clarke 2009), and this prompted us to examine the arginine methylome of T. brucei to ask if the same is true in this early-branching eukaryote. Indeed, in a global proteomics screen in T. brucei , we identified 136 RNA-binding and metabolic proteins harboring arginine methylmarks (Fisk et al. 2013; Lott et al. 2013). "
ABSTRACT: Arginine methylation is a common posttranslational modification that has far-reaching cellular effects. Trypanosoma brucei is an early-branching eukaryote with four characterized protein arginine methyltransferases (PRMTs), one additional putative PRMT, and over 800 arginine methylated proteins, suggesting that arginine methylation has widespread impacts in this organism. While much is known about the activities of individual T. brucei PRMTs (TbPRMTs), little is known regarding how TbPRMTs function together in vivo. In this study, we analyzed single and selected double TbPRMT knockdowns for the impact on expression of TbPRMTs and global methylation status. Repression of TbPRMT1 caused a decrease in asymmetric dimethylarginine and a marked increase in monomethylarginine that was catalyzed by TbPRMT7, suggesting that TbPRMT1 and TbPRMT7 can compete for the same substrate. We also observed an unexpected and strong interdependence between TbPRMT1 and TbPRMT3 protein levels. This finding, together with the observation of similar methyl landscape profiles in TbPRMT1 and TbPRMT3 repressed cells, strongly suggests that these two enzymes form a functional complex. We show that corepression of TbPRMT6/7 synergistically impacts growth of procyclic-form T. brucei. Our findings also implicate the actions of noncanonical, and as yet unidentified, PRMTs in T. brucei. Together, our studies indicate that TbPRMTs display a functional interplay at multiple levels.MicrobiologyOpen 10/2014; 3(5). DOI:10.1002/mbo3.191 · 2.21 Impact Factor
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- "The change of arginine side chain guanidino groups is quantitatively one of the most extensive protein methylation reactions in mammalian cells . Arginine is unique among amino acids as its guanidino group contains five potential hydrogen bond donors that are positioned for favorable interactions with biological hydrogen bond acceptors  . "
ABSTRACT: α-Defensins (e.g. human neutrophil peptides, HNPs) have a broad spectrum bactericidal activity contributing to human innate immunity. The positive charge of amino acid side chains is responsible for the first interaction of cationic antimicrobial peptides with negatively charged bacterial membranes. α-Defensins contain a high content of Arg residues compared to Lys. In this paper, different peptide analogs including substitution of Arg-14 respectively with N(G)-N(G')-asymmetric dimethyl-l-arginine (ADMA), N(G)-N(G')-symmetric dimethyl-l-arginine (SDMA) and Lys (R14K and R15KR14KR15K) variants have been studied to test the role of Arg guanidino group and the localized cationic charge of Lys for interaction with lipid membranes. Our findings show that all the variants have a decreased disruptive activity against the bilayer. The methylated analogs show a reduction in membrane partitioning due to the lack of their ability to form hydrogen bonds. Comparison with the native HNP-1 peptide has been discussed.Biophysical chemistry 04/2014; 190-191C:32-40. DOI:10.1016/j.bpc.2014.04.003 · 2.32 Impact Factor
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- "The generation of asymmetric N G , N G -dimethylarginine (ADMA) is catalyzed by type I enzymes, whereas type II enzymes catalyze the formation of symmetric N G ,N ′G dimethylarginine (SDMA) . PRMTs target numerous proteins involved in transcriptional regulation, signal transduction, RNA metabolism and DNA repair . Particularly, histone targeting by PRMTs is an important epigenetic mechanism of gene expression regulation. "
ABSTRACT: Accumulation of S-adenosylhomocysteine (AdoHcy), the homocysteine (Hcy) precursor and a potent methyltransferase inhibitor, may mediate the neurological and vascular complications associated with elevated Hcy. Protein arginine methylation is a crucial post-translational modification and generates monomethylarginine (MMA) and dimethylarginine (asymmetric, ADMA, and symmetric, SDMA) residues. We aimed at determining whether protein arginine methylation status is disturbed in an animal model of diet-induced hyperhomocysteinemia (HHcy). HHcy was achieved by dietary manipulation of Wistar rats: methionine-enrichment (HM), B vitamins deficiency (LV), or both (HMLV). Total Hcy, S-adenosylmethionine (AdoMet), AdoHcy, and MMA, ADMA and SDMA concentrations in plasma or tissues (heart, brain and liver) were determined by adequate HPLC or LC-ESI-MS/MS methods. Moreover, in tissues from the HMLV group, histone arginine asymmetric dimethylation was evaluated by Western blotting, and the histone methylation marks H3R17me2a, H3R8me2a and H4R3me2a were studied. HHcy was induced by all special diets, with elevation of AdoHcy concentrations in liver (LV and HMLV) and heart (HMLV) (all versus control). Plasma ADMA levels were lower in all hyperhomocysteinemic animals. Protein-incorporated ADMA levels were decreased in brain and in heart (both for the LV and HMLV groups). Moreover, in brain of animals exposed to the HMLV diet, the H3R8me2a mark was profoundly decreased. In conclusion, our results show that diet-induced Hcy elevation disturbs global protein arginine methylation in a tissue-specific manner and affects histone arginine methylation in brain. Future research is warranted to disclose the functional implications of the global protein and histone arginine hypomethylation triggered by Hcy elevation.Biochimica et Biophysica Acta 05/2013; 1832(10). DOI:10.1016/j.bbadis.2013.05.013 · 4.66 Impact Factor