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PRMT9 is a Type II methyltransferase that methylates the splicing factor SAP145

2015; Nature Portfolio; Volume: 6; Issue: 1 Linguagem: Inglês

10.1038/ncomms7428

2041-1723

Yanzhong Yang, Andrea Hadjikyriacou, Zheng Xia, Sitaram Gayatri, Daehoon Kim, Cecilia I. Zurita‐Lopez, Ryan L. Kelly, Ailan Guo, Wei Li, Steven Clarke, Mark T. Bedford,

Epigenetics and DNA Methylation

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. Protein arginine methylation is an abundant post-translational modification often associated with RNA-binding proteins. Here the authors show that the previously uncharacterized PRMT9 enzyme catalyses the symmetrical methylation of SAP145, which promotes its association with the SMN complex and regulates splicing.