S-nitrosylation of Protein arginine methyltransferase (PRMT)1 regulates protein arginine dimethylation level
Upregulation of Nitric oxide (NO) contributes to the pathogenesis of numerous diseases such as neurodegenerative diseases and cancer via s-nitrosylation, a post-translational modification of proteins. In recent years, it has become increasingly clear that NO has an epigenetic function in regulating gene expression, but the full extent of this function is still unknown. We found that the enzymatic activity of PRMT1, a major asymmetric arginine methyltransferase for histones and many RNA metabolic proteins, is attenuated by NO. We found that NO mainly S-nitrosylated 119 cysteine residues sterically close to the enzyme active site of PRMT1 and attenuates its activity. Furthermore, we identified DDX3 as a substrate of PRMT1 interactome by Bio-ID. Arginine methylation of DDX3 induced by PRMT1 is attenuated by NO treatment. Our results suggest that there may be a relationship between NO-induced stress and metabolic decay of RNA, suggesting the existence of a novel epigenetic regulatory system.