Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Caenorhabditis elegans / enzymology
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism
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Carrier Proteins / metabolism
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Cell Adhesion Molecules / metabolism
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Cloning, Molecular
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DNA Helicases
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DNA-Binding Proteins
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Drosophila Proteins*
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Genes, Helminth
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Histone Deacetylases / genetics
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Histone Deacetylases / isolation & purification
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Histone Deacetylases / metabolism
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Humans
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In Vitro Techniques
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Mice
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Molecular Sequence Data
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Nuclear Proteins / isolation & purification*
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Nuclear Proteins / metabolism*
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Nuclear Receptor Co-Repressor 1
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / isolation & purification*
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Protein Serine-Threonine Kinases / metabolism*
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Proteins / metabolism
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RNA Processing, Post-Transcriptional
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RNA Splicing
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RNA Splicing Factors
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RNA-Binding Proteins
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Repressor Proteins / isolation & purification*
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Repressor Proteins / metabolism*
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Ribonucleoprotein, U4-U6 Small Nuclear / genetics
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Ribonucleoprotein, U4-U6 Small Nuclear / isolation & purification*
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Ribonucleoprotein, U4-U6 Small Nuclear / metabolism*
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Ribonucleoprotein, U5 Small Nuclear / isolation & purification*
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Ribonucleoprotein, U5 Small Nuclear / metabolism*
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Schizosaccharomyces / enzymology
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Schizosaccharomyces pombe Proteins*
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Transcription Factors / metabolism
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Transcription, Genetic
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Two-Hybrid System Techniques
Substances
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Caenorhabditis elegans Proteins
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Carrier Proteins
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Cell Adhesion Molecules
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DNA-Binding Proteins
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Drosophila Proteins
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NCOR1 protein, human
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Ncor1 protein, mouse
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Nuclear Proteins
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Nuclear Receptor Co-Repressor 1
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PNN protein, human
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PRPF6 protein, human
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Pnn protein, mouse
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Proteins
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RNA Splicing Factors
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RNA-Binding Proteins
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Repressor Proteins
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Ribonucleoprotein, U4-U6 Small Nuclear
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Ribonucleoprotein, U5 Small Nuclear
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SFSWAP protein, human
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Schizosaccharomyces pombe Proteins
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Sfswap protein, mouse
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Transcription Factors
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su(wa) protein, Drosophila
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PRPF4B protein, human
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Protein Serine-Threonine Kinases
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Prpf4b protein, mouse
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prp4 protein, S pombe
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Histone Deacetylases
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SMARCA4 protein, human
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Smarca4 protein, mouse
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DNA Helicases
Associated data
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GENBANK/AF283465
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GENBANK/AF283466