2. Academic Validation
  3. PRMT9 is a type II methyltransferase that methylates the splicing factor SAP145

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

  • Nat Commun. 2015 Mar 4;6:6428. doi: 10.1038/ncomms7428.
Yanzhong Yang 1,  Andrea Hadjikyriacou 2,  Zheng Xia 3,  Sitaram Gayatri 4,  Daehoon Kim 4,  Cecilia Zurita-Lopez 2,  Ryan Kelly 2,  Ailan Guo 5,  Wei Li 3,  Steven G Clarke 2,  Mark T Bedford 4
Affiliations

Affiliations

  • 1 1] Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas 78957, USA [2] Department of Radiation Biology, Beckman Research Institute, City of Hope Cancer Center, Duarte, California 91010, USA.
  • 2 Department of Chemistry and Biochemistry, Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA.
  • 3 Division of Biostatistics, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
  • 4 Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas 78957, USA.
  • 5 Cell Signaling Technology Inc., Danvers, Massachusetts 01923, USA.
PMID: 25737013 DOI: 10.1038/ncomms7428
Abstract

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.

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