Protein arginine methyltransferase 6 is a novel substrate of protein arginine methyltransferase 1

BACKGROUND Post-translational modifications play key roles in various biological processes.Protein arginine methyltransferases(PRMTs)transfer the methyl group to specific arginine residues.Both PRMT1 and PRMT6 have emerges as crucial factors in the development and progression of multiple cancer types.We posit that PRMT1 and PRMT6 might interplay directly or in-directly in multiple ways accounting for shared disease phenotypes.AIM To investigate the mechanism of the interaction between PRMT1 and PRMT6.METHODS Gel electrophoresis autoradiography was performed to test the methyltranferase activity of PRMTs and characterize the kinetics parameters of PRMTs.Liquid chromatography-tandem mass spectrometryanalysis was performed to detect the PRMT6 methylation sites.RESULTS In this study we investigated the interaction between PRMT1 and PRMT6,and PRMT6 was shown to be a novel substrate of PRMT1.We identified specific arginine residues of PRMT6 that are methylated by PRMT1,with R106 being the major methylation site.Combined biochemical and cellular data showed that PRMT1 downregulates the enzymatic activity of PRMT6 in histone H3 methylation.CONCLUSION PRMT6 is methylated by PRMT1 and R106 is a major methylation site induced by PRMT1.PRMT1 methylation suppresses the activity of PRMT6.

PRMT6 physically associates with nuclear factor Y to regulate photoperiodic flowering in Arabidopsis

The timing of floral transition is critical for reproductive success in flowering plants.In long-day(LD)plant Arabidopsis,the floral regulator gene FLOWERING LOCUS T(FT)is a major component of the mobile florigen.FT expression is rhythmically activated by CONSTANS(CO),and specifically accumu-lated at dusk of LDs.However;the underlying mechanism of adequate regulation of FT transcription in response to day-length cues to warrant flowering time still remains to be investigated.Here,we identify a homolog of human protein arginine methyltransferases 6(HsPRMT6)in Arabidopsis,and confirm AtPRMT6 physically interacts with three positive regulators of flowering Nuclear Factors YC3(NF-YC3),NF-YC9,and NF-YB3.Further investigations find that AtPRMT6 and its encoding protein accumulate at dusk of LDs.PRMT6-mediated H3 R2me2a modification enhances the promotion of NF-YCs on FT transcription in response to inductive LD signals.Moreover,AtPRMT6 and its homologues proteins AtPRMT4a and AtPRMT4b coordinately inhibit the expression of FLOWERING LOCUS C,a suppressor of FT.Taken together,our study reveals the role of arginine methylation in photoperiodic pathway and how the PRMT6-mediating H3R2me2a system interacts with NF-CO module to dynamically control FT expression and facilitate flowering time.