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PLoS Genet. 2015 Mar 31;11(3):e1005074. doi: 10.1371/journal.pgen.1005074. eCollection 2015 Mar.

Genetic interaction mapping reveals a role for the SWI/SNF nucleosome remodeler in spliceosome activation in fission yeast.

Author information

1
Department of Biochemistry and Biophysics, University of California, San Francisco, California, United States of America.
2
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.
3
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.
4
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, United States of America.
5
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.

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.

PMID:
25825871
PMCID:
PMC4380400
DOI:
10.1371/journal.pgen.1005074
[Indexed for MEDLINE]
Free PMC Article

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