title: Genetic interaction mapping reveals a role for the SWI/SNF nucleosome remodeler in spliceosome activation in fission yeast.
abstract: Although numerous regulatory connections between pre-mRNA splicing and chromatin have been demonstrated, the precise mechanisms by which chromatin factors influence spliceosome assembly and/or catalysis remain unclear. To probe the genetic network of pre-mRNA splicing in the fission yeast Schizosaccharomyces pombe, we constructed an epistatic mini-array profile (E-MAP) and discovered many new connections between chromatin and splicing. Notably, the nucleosome remodeler SWI/SNF had strong genetic interactions with components of the U2 snRNP SF3 complex. Overexpression of SF3 components in ΔSWI/SNF cells led to inefficient splicing of many fission yeast introns, predominantly those with non-consensus splice sites. Deletion of SWI/SNF decreased recruitment of the splicing ATPase Prp2, suggesting that SWI/SNF promotes co-transcriptional spliceosome assembly prior to first step catalysis. Importantly, defects in SWI/SNF as well as SF3 overexpression each altered nucleosome occupancy along intron-containing genes, illustrating that the chromatin landscape both affects--and is affected by--co-transcriptional splicing.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, California, United States of America.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Patrick
authors.affiliation: Systems Biology Ireland, University College Dublin, Dublin, Ireland; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, United States of America; California Institute for Quantitative Biosciences, QB3, San Francisco, California, United States of America.
authors.forename: Colm J
authors.initials: CJ
authors.lastname: Ryan
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, United States of America; California Institute for Quantitative Biosciences, QB3, San Francisco, California, United States of America.
authors.forename: Jiewei
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, United States of America.
authors.forename: Jesse J
authors.initials: JJ
authors.lastname: Lipp
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, California, United States of America.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Nissen
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, United States of America.
authors.forename: Assen
authors.initials: A
authors.lastname: Roguev
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, United States of America; California Institute for Quantitative Biosciences, QB3, San Francisco, California, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Shales
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, United States of America; California Institute for Quantitative Biosciences, QB3, San Francisco, California, United States of America; J. David Gladstone Institutes, San Francisco, California, United States of America.
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, California, United States of America.
authors.forename: Christine
authors.initials: C
authors.lastname: Guthrie
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D002843:Chromatin / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D007438:Introns / Q000235:genetics; D009707:Nucleosomes / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012326:RNA Splicing / Q000235:genetics*; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics*; D012568:Schizosaccharomyces / Q000235:genetics; D017381:Spliceosomes / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D009707:Nucleosomes; D017413:Ribonucleoprotein, U2 Small Nuclear; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; D000251:Adenosine Triphosphatases
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