PRMT8: Characterization of a novel neuron-specific protein arginine methyltransferase

Abstract

Methylation of arginine residues is a post-translational modification mediated by specific enzymes known as the Protein Arginine Methyltransferase (PRMT) family. In this thesis, we present our research on PRMT8, an enzyme catalyzing the formation of asymmetric dimethylarginine (aDMA), which displays a unique distribution at the plasma membrane of neuronal cells of the central nervous system (CNS). An ontogenic analysis of PRMT8 in mouse tissues revealed that its expression in the brain is induced during the perinatal stage and is maintained in adulthood. The P19 cell line was identified as a valid model for endogenous PRMT8 and showed the induction and requirement of PRMT8 to achieve neuronal processes. A P19 PRMT8 knock-down cell line does not survive neuronal differentiation while, in contrast, no cell death is observed when the muscle lineage is induced. Taken together, these findings suggest an important role for PRMT8 in neuronal differentiation and/or function in the CNS.