The Zheng group recently reported a mechanism finding on protein arginine methyltransferase (PRMT) in the journal World J Biol Chem (2023, 14, 84-98. doi: 10.4331/wjbc.v14.i5.84).
In this work, graduate students Mengtong Cao and You Feng discovered a new heteromeric interaction between two members of the PRMT family, PRMT1 and PRMT6. Intriguingly, PRMT6 undergoes methylation by PRMT1, which makes it be a ‘modified modifier’. Extensive experimental studies were performed to illuminate the mechanism and functional outcome of PRMT1-PRMT6 interaction, ranged from liquid chromatography with LC-MS/MS analysis, site-directed mutagenesis studies, steady-state kinetics, biochemical tests, cellular transfection, affinity pulldown, to western blotting. The results for the first time demonstrated that one PRMT member modulates another member’s enzymatic activity through the mechanism of covalent posttranslational modification. This work illustrates the complex dynamic cross-talking relationship within the PRMT family and provides a new understanding of the regulatory mechanisms underlying protein arginine methylation.