title: Prp4 Kinase Grants the License to Splice: Control of Weak Splice Sites during Spliceosome Activation.
abstract: The genome of the fission yeast Schizosaccharomyces pombe encodes 17 kinases that are essential for cell growth. These include the cell-cycle regulator Cdc2, as well as several kinases that coordinate cell growth, polarity, and morphogenesis during the cell cycle. In this study, we further characterized another of these essential kinases, Prp4, and showed that the splicing of many introns is dependent on Prp4 kinase activity. For detailed characterization, we chose the genes res1 and ppk8, each of which contains one intron of typical size and position. Splicing of the res1 intron was dependent on Prp4 kinase activity, whereas splicing of the ppk8 intron was not. Extensive mutational analyses of the 5' splice site of both genes revealed that proper transient interaction with the 5' end of snRNA U1 governs the dependence of splicing on Prp4 kinase activity. Proper transient interaction between the branch sequence and snRNA U2 was also important. Therefore, the Prp4 kinase is required for recognition and efficient splicing of introns displaying weak exon1/5' splice sites and weak branch sequences.
authors.affiliation: Institute of Genetics, Technische Universität Braunschweig, Braunschweig, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Eckert
authors.affiliation: Institute of Genetics, Technische Universität Braunschweig, Braunschweig, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Andrée
authors.affiliation: Department of Physiology and Pathophysiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: Aleh
authors.initials: A
authors.lastname: Razanau
authors.affiliation: Institute of Genetics, Technische Universität Braunschweig, Braunschweig, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Zock-Emmenthal
authors.affiliation: Institute of Genetics, Technische Universität Braunschweig, Braunschweig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Lützelberger
authors.affiliation: Institute of Genetics, Technische Universität Braunschweig, Braunschweig, Germany.
authors.forename: Susann
authors.initials: S
authors.lastname: Plath
authors.affiliation: Institute of Genetics, Technische Universität Braunschweig, Braunschweig, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Guerra-Moreno
authors.affiliation: CRG Bioinformatics Core, Centre de Regulació Genòmica (CRG), and Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Luca
authors.initials: L
authors.lastname: Cozzuto
authors.affiliation: Oxidative Stress and Cell Cycle Group, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Ayté
authors.affiliation: Institute of Genetics, Technische Universität Braunschweig, Braunschweig, Germany.
authors.forename: Norbert F
authors.initials: NF
authors.lastname: Käufer
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics; D007438:Introns / Q000235:genetics; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D000072260:RNA Splicing Factors; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000235:genetics*; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics; D012568:Schizosaccharomyces / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics*; D017381:Spliceosomes / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D022821:RNA Splice Sites; D000072260:RNA Splicing Factors; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; C078732:res1 protein, S pombe; D017346:Protein Serine-Threonine Kinases; C489981:prp4 protein, S pombe