Tsukuba, Japan—Immune function is regulated not only through gene activation and repression but also through various chemical modifications of intracellular proteins. One such modification is arginine methylation, in which methyl groups are added to arginine residues within proteins. In this review, the researchers synthesize recent evidence showing how PRMT family enzymes regulate gene expression, RNA metabolism, immune signaling, tumor immunity, and age-related chronic inflammation. Further, they discuss potential therapeutic strategies for immune-related diseases.
The researchers also highlight the regulatory roles of PRMTs via mechanisms independent of their methylation activity. To integrate these distinct roles of PRMTs, the researchers propose a three-tiered framework comprising methylation of histone and non-histone proteins (Layer 1), generation of free methylarginines through the turnover of methylated proteins (Layer 2), and methyltransferase-independent functions in which PRMTs modulate cellular processes through RNA and protein interactions (Layer 3). This model provides insights into the link between intracellular protein regulation and broader physiological processes, including immune responses, metabolism, and vascular homeostasis.
