The methylation induced by protein arginine methyltransferase 5 promotes tumorigenesis and progression of lung cancer

Post-translational modification (PTM) is involved in regulating many biological processes. The methylation of arginine residues is a common form of PTM, which is catalyzed by a distinct group of transmethylases known as the protein arginine methyltransferases (PRMTs). PRMTs widely exist in eukaryotic cells and participate in epigenetic regulation through the methylation of arginine residues of histone and/or transcription factors. In particular, such methylation modifications are performed by PRMTs, which catalyze and transfer methyl group (CH3) from S-adenosylmethionine (SAM) to the guanidine nitrogen of arginine residues. At present, PRMTs are classified into two subgroups according to the types of methylation they catalyze (Figure 1), namely type I and type II. The former one includes PRMT1, 2, 3, 4, 6, and 8, catalyze the formation of ω-NG-monomethyl arginine (MMA) and ω-NG, NG-asymmetric dimethylarginine (aDMA) (1-5), while the latter one covers PRMT5, 7, and 9, generate MMA and ω-NG, N'G-symmetric dimethylarginine (sDMA) residues (6). With each addition of CH3 to the guanidine nitrogen of arginine residues, a potential hydrogen bond donor would be removed, which further alters the structure of the target proteins. Both aDMA and sDMA, for example, can diversify the hydrophobicity and bulkiness of a target protein, which accordingly impact the protein-protein interaction, RNA processing, DNA repair, transduction of intracellular signaling, and regulation of gene expression