The arginine methyltransferase CARM1 regulates the coupling of transcription and mRNA processing.
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.
Pubmed ID: 17218272 RIS Download
Alternative Splicing | Amino Acid Motifs | Animals | Antibodies | Exons | Histones | Humans | Methylation | Mice | Nuclear Proteins | Protein Binding | Protein Methyltransferases | Protein Structure, Tertiary | Protein-Arginine N-Methyltransferases | RNA Processing, Post-Transcriptional | RNA, Messenger | Substrate Specificity | Transcription Factors | Transcription, Genetic