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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


  • Dellaire G
  • Makarov EM
  • Cowger JJ
  • Longman D
  • Sutherland HG
  • L├╝hrmann R
  • Torchia J
  • Bickmore WA


Molecular and cellular biology

Publication Data

July 21, 2002

Associated Grants


Mesh Terms

  • 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