The Influence of Arginine Methylation in Immunity and Inflammation

Abstract

Exploration in the field of epigenetics has revealed that protein arginine methyltransferases (PRMTs) contribute to disease, and this has given way to the development of specific small molecule compounds that inhibit arginine methylation. Protein arginine methylation is known to regulate fundamental cellular processes, such as transcription; pre-mRNA splicing and other RNA processing mechanisms; signal transduction, including the anti-viral response; and cellular metabolism. PRMTs are also implicated in the regulation of physiological processes, including embryonic development, myogenesis, and the immune system. Finally, the dysregulation of PRMTs is apparent in cancer, neurodegeneration, muscular disorders, and during inflammation. Herein, we review the functions of PRMTs in immunity and inflammation. We also discuss recent progress with PRMTs regarding the modulation of gene expression related to T and B lymphocyte differentiation, germinal center dynamics, and anti-viral signaling responses, as well as the clinical relevance of using PRMT inhibitors alone or in combination with other drugs to treat cancer, immune, and inflammatory-related diseases.

The 2022 Lady Estelle Wolfson lectureship on neurofilaments

“…Citrullination reduces charge (−1 per deimination), weight (+0.98 mW), susceptibility to proteolysis, structure, function, neurodegeneration and autoimmunity (Briot et al, 2020). Given the amount of data on citrullination of human MBP (Cao et al, 1998; Srour et al, 2022; Wang, Chen, et al, 2022; Yu & Proost, 2022), which has only 29 Arg residues, it is surprising how little is known regarding the citrullination of human NfH (44 Arg), NfM (37 Arg), NfL (35 Arg), INA (45 Arg), PRPH (48 Arg). Citrullination in Figure 2 was modelled in orange spheres.…”

“…Gly is a frequent donor for the amide. Other mechanisms are methylation and isoprenylation for GPI anchors and ADP‐dependent ribosylation of C‐terminal Lys (Dutour‐Provenzano & Etienne‐Manneville, 2021; Srour et al, 2022; Ying & Li, 2022).…”

Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

“… 769 Moreover, selectively inhibiting PRMT5 may prove to be an effective therapeutic strategy for RA and ulcerative colitis. 768 PRMT7 is an essential contributor to B cell lymphomagenesis. 768 FOXP3, a TF critical for Treg cell identity and immunosuppressive function, is dimethylated by PRMT5 (or PRMT1, PRMT6) at R48 and R51.…”

“… 768 PRMT7 is an essential contributor to B cell lymphomagenesis. 768 FOXP3, a TF critical for Treg cell identity and immunosuppressive function, is dimethylated by PRMT5 (or PRMT1, PRMT6) at R48 and R51. This methylation reduces the expression of immunosuppressive genes, consequently leading to autoimmunity, tumor shrinkage, and associated CD8 + T cell infiltration.…”

Disease Tolerance Acquired Through RepeatedPlasmodiumInfection Involves Epigenetic Reprogramming of Innate Immune Cells

“…Finally, arginine dimethylation (Rme2asy, Rme2sym) was also more prevalent during asymptomatic infection (Figure 3A,D). This post-translational modification, in its asymmetric form, has primarily been shown to negatively regulate inflammation 26 . The differential regulation of these epigenetic markers across disease states is as would be predicted based on the differential expression of RNA encoding their writers (Figure 1G) and alludes to the possibility that the epigenetic state associated with asymptomatic infection may negatively regulate cytokine production.…”