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

Nat Commun. 2015 Mar 4;6:6428. doi: 10.1038/ncomms7428.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arginine / analogs & derivatives*
  • Arginine / genetics
  • Arginine / metabolism
  • Base Sequence
  • Binding Sites / genetics
  • Chromatography, Ion Exchange
  • Chromatography, Thin Layer
  • DNA Methylation / genetics
  • DNA Methylation / physiology*
  • DNA Primers / genetics
  • F-Box Proteins / metabolism*
  • Fluorescent Antibody Technique
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunoprecipitation
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein-Arginine N-Methyltransferases / metabolism*
  • RNA Splicing Factors
  • RNA-Binding Proteins / metabolism*
  • Sequence Alignment
  • Sequence Analysis, RNA
  • Survival of Motor Neuron 1 Protein / genetics


  • DNA Primers
  • F-Box Proteins
  • RNA Splicing Factors
  • RNA-Binding Proteins
  • SF3B2 protein, human
  • Survival of Motor Neuron 1 Protein
  • symmetric dimethylarginine
  • Arginine
  • FBXO11 protein, human
  • Protein-Arginine N-Methyltransferases