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Molecular and Cellular Biology, July 2002, p. 5141-5156, Vol. 22, No. 14
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.14.5141-5156.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mammalian PRP4 Kinase Copurifies and Interacts with Components of Both the U5 snRNP and the N-CoR Deacetylase Complexes

Graham Dellaire,1 Evgeny M. Makarov,2 JeffJ.M. Cowger,3 Dasa Longman,1 Heidi G. E. Sutherland,1 Reinhard Lührmann,2 Joseph Torchia,3 and Wendy A. Bickmore1*

MRC-Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom,1 Department of Cellular Biochemistry, Max-Planck-Institute for Biophysical Chemistry, Gottingen, Germany,2 Department of Pharmacology and Toxicology and Oncology, Cancer Research Laboratories, London Regional Cancer Centre, The University of Western Ontario, London, Ontario, Canada3

Received 8 March 2002/ Accepted 11 April 2002

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.

* Corresponding author. Mailing address: MRC-Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, United Kingdom. Phone: 44 (131) 467-8418. Fax: 44 (131) 343-2620. E-mail: Wendy.Bickmore{at}hgu.mrc.ac.uk.

Molecular and Cellular Biology, July 2002, p. 5141-5156, Vol. 22, No. 14
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.14.5141-5156.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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