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.
Mesh Terms:
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
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
Mol. Cell
Date: Jan. 12, 2007
PubMed ID: 17218272
View in: Pubmed Google Scholar
Download Curated Data For This Publication
104084
Switch View:
- Interactions 13