NF90/NFAR (nuclear factors associated with dsRNA) - a new methylation substrate of the PRMT5-WD45-RioK1 complex

Protein-arginine methylation is a common posttranslational modification, crucial to various cellular processes, such as protein-protein interactions or binding to nucleic acids. The central enzyme of symmetric protein arginine methylation in mammals is the protein arginine methyltransferase 5 (PRMT5). While the methylation reaction itself is well understood, recruitment and differentiation among substrates remain less clear. One mechanism to regulate the diversity of PRMT5 substrate recognition is the mutual binding to the adaptor proteins pICln or RioK1. Here, we describe the specific interaction of Nuclear Factor 90 (NF90) with the PRMT5-WD45-RioK1 complex. We show for the first time that NF90 is symmetrically dimethylated by PRMT5 within the RG-rich region in its C-terminus. Since upregulation of PRMT5 is a hallmark of many cancer cells, the characterization of its dimethylation and modulation by specific commercial inhibitors in vivo presented here may contribute to a better understanding of PRMT5 function and its role in cancer.

Automated summary

Protein-arginine methylation is a common posttranslational modification essential to cellular processes, with PRMT5 playing a central role in mammals. The study explores the specific interaction of NF90 with the PRMT5-WD45-RioK1 complex and reveals the symmetrical dimethylation of NF90 by PRMT5. Understanding PRMT5 function and its modulation by commercial inhibitors in cancer cells could provide insight into its role in cancer.