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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Chromatin / genetics
  • Chromosomal Proteins, Non-Histone / genetics*
  • Gene Expression Regulation, Fungal
  • Gene Regulatory Networks*
  • Introns / genetics
  • Nucleosomes / genetics*
  • Nucleosomes / metabolism
  • Promoter Regions, Genetic
  • RNA Splicing / genetics*
  • Ribonucleoprotein, U2 Small Nuclear / genetics*
  • Schizosaccharomyces / genetics
  • Spliceosomes / genetics*
  • Spliceosomes / metabolism
  • Transcription Factors / genetics*
  • Transcription, Genetic

Substances

  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Nucleosomes
  • Ribonucleoprotein, U2 Small Nuclear
  • SWI-SNF-B chromatin-remodeling complex
  • Transcription Factors
  • Adenosine Triphosphatases