Doi:10.1242/jcs.019885 Arginine methylation is a prevalent post-translational modification found on both nuclear and cytoplasmic proteins. The methylation of arginine residues is catalyzed by the protein arginine N-methyltransferase (PRMT) family of Methylation of arginine residues H 2N H 3N Arginine-methylated proteins Chromatin-associated proteins hnRNPs and spicing proteins Other mRNA-binding proteins DNA damage response proteins Nucleolar and ribosomal proteins Viral proteins Signalling proteins C N

The human genome encodes a family of nine protein arginine methyltransferases (PRMT1–9), whose members can catalyse three distinct types of methylation on arginine residues. Here we identify two spliceosome-associated proteins—SAP145 and SAP49—as PRMT9-binding partners, linking PRMT9 to U2 snRNP maturation. We show that SAP145 is methylated by PRMT9 at arginine 508, which takes the form of monomethylated arginine (MMA) and symmetrically dimethylated arginine (SDMA). PRMT9 thus joins PRMT5 as the only mammalian enzymes capable of depositing the SDMA mark. Methylation of SAP145 on Arg 508 generates a binding site for the Tudor domain of the Survival of Motor Neuron (SMN) protein, and RNA-seq analysis reveals gross splicing changes when PRMT9 levels are attenuated. These results identify PRMT9 as a nonhistone methyltransferase that primes the U2 snRNP for interaction with SMN.