The arginine methyltransferase CARM1 regulates the coupling of transcription and mRNA processing

Mol Cell. 2007 Jan 12;25(1):71-83. doi: 10.1016/j.molcel.2006.11.019.


The coactivator-associated arginine methyltransferase CARM1 is recruited by many different transcription factors as a positive regulator. To understand the mechanism by which CARM1 functions, we sought to isolate its substrates. We developed a small-pool screening approach for this purpose and identified CA150, SAP49, SmB, and U1C as splicing factors that are specifically methylated by CARM1. We further showed that CA150, a molecule that links transcription to splicing, interacts with the Tudor domain of the spinal muscular atrophy protein SMN in a CARM1-dependent fashion. Experiments with an exogenous splicing reporter and the endogenous CD44 gene revealed that CARM1 promotes exon skipping in an enzyme-dependent manner. The identification of splicing factors that are methylated by CARM1, and protein-protein interactions that are regulated by CARM1, strongly implicates this enzyme in the regulation of alternative splicing and points toward its involvement in spinal muscular atrophy pathogenesis.

Publication types

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

MeSH terms

  • Alternative Splicing / genetics
  • Amino Acid Motifs
  • Animals
  • Antibodies / immunology
  • Exons / genetics
  • Histones / immunology
  • Humans
  • Methylation
  • Mice
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Protein Methyltransferases / metabolism
  • Protein Structure, Tertiary
  • Protein-Arginine N-Methyltransferases / chemistry
  • Protein-Arginine N-Methyltransferases / deficiency
  • Protein-Arginine N-Methyltransferases / metabolism*
  • RNA Processing, Post-Transcriptional*
  • RNA, Messenger / metabolism*
  • Substrate Specificity
  • Transcription Factors / metabolism
  • Transcription, Genetic*


  • Antibodies
  • Histones
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • Protein Methyltransferases
  • Protein-Arginine N-Methyltransferases
  • coactivator-associated arginine methyltransferase 1