title: Mammalian PRP4 kinase copurifies and interacts with components of both the U5 snRNP and the N-CoR deacetylase complexes.
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.
authors.affiliation: MRC-Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Dellaire
authors.forename: Evgeny M
authors.initials: EM
authors.lastname: Makarov
authors.forename: Jeff J M
authors.initials: JJ
authors.lastname: Cowger
authors.forename: Dasa
authors.initials: D
authors.lastname: Longman
authors.forename: Heidi G E
authors.initials: HG
authors.lastname: Sutherland
authors.forename: Reinhard
authors.initials: R
authors.lastname: Lührmann
authors.forename: Joseph
authors.initials: J
authors.lastname: Torchia
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Bickmore
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003001:Cloning, Molecular; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D017238:Genes, Helminth; D006655:Histone Deacetylases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000302:isolation & purification* / Q000378:metabolism*; D056971:Nuclear Receptor Co-Repressor 1; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000302:isolation & purification* / Q000378:metabolism*; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D017415:Ribonucleoprotein, U5 Small Nuclear / Q000302:isolation & purification* / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000201:enzymology; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C539127:NCOR1 protein, human; C539128:Ncor1 protein, mouse; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; C102646:PNN protein, human; C408605:PRPF6 protein, human; C491175:Pnn protein, mouse; D011506:Proteins; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D017415:Ribonucleoprotein, U5 Small Nuclear; C484205:SFSWAP protein, human; D029702:Schizosaccharomyces pombe Proteins; C484206:Sfswap protein, mouse; D014157:Transcription Factors; C087691:su(wa) protein, Drosophila; C489984:PRPF4B protein, human; D017346:Protein Serine-Threonine Kinases; C489983:Prpf4b protein, mouse; C489981:prp4 protein, S pombe; D006655:Histone Deacetylases; C084108:SMARCA4 protein, human; C513194:Smarca4 protein, mouse; D004265:DNA Helicases