Mammalian PRP4 kinase copurifies and interacts with components of both the U5 snRNP and the N-CoR deacetylase complexes.
A growing body of evidence supports the coordination of pre-mRNA processing and transcriptional regulation. We demonstrate here that mammalian PRP4 kinase (PRP4K) is associated with complexes involved in both of these processes. PRP4K is implicated in pre-mRNA splicing as the homologue of the Schizosaccharomyces pombe pre-mRNA splicing kinase Prp4p, and it is enriched in SC35-containing nuclear splicing speckles. RNA interference of Caenorhabditis elegans PRP4K indicates that it is essential in metazoans. In support of a role for PRP4K in pre-mRNA splicing, we identified PRP6, SWAP, and pinin as interacting proteins and demonstrated that PRP4K is a U5 snRNP-associated kinase. In addition, BRG1 and N-CoR, components of nuclear hormone coactivator and corepressor complexes, also interact with PRP4K. PRP4K coimmunoprecipitates with N-CoR, BRG1, pinin, and PRP6, and we present data suggesting that PRP6 and BRG1 are substrates of this kinase. Lastly, PRP4K, BRG1, and PRP6 can be purified as components of the N-CoR-2 complex, and affinity-purified PRP4K/N-CoR complexes exhibit deacetylase activity. We suggest that PRP4K is an essential kinase that, in association with the both U5 snRNP and N-CoR deacetylase complexes, demonstrates a possible coordination of pre-mRNA splicing with chromatin remodeling events involved in transcriptional regulation.
Pubmed ID: 12077342 RIS Download
Amino Acid Sequence | Animals | Caenorhabditis elegans | Caenorhabditis elegans Proteins | Carrier Proteins | Cell Adhesion Molecules | Cloning, Molecular | DNA Helicases | Drosophila Proteins | Genes, Helminth | Histone Deacetylases | Humans | In Vitro Techniques | Mice | Molecular Sequence Data | Nuclear Proteins | Nuclear Receptor Co-Repressor 1 | Protein-Serine-Threonine Kinases | Proteins | RNA Processing, Post-Transcriptional | RNA Splicing | RNA-Binding Proteins | Repressor Proteins | Ribonucleoprotein, U4-U6 Small Nuclear | Ribonucleoprotein, U5 Small Nuclear | Schizosaccharomyces | Schizosaccharomyces pombe Proteins | Transcription Factors | Transcription, Genetic | Two-Hybrid System Techniques