Genetic Interaction Mapping Reveals a Role for the SWI/SNF Nucleosome Remodeler in Spliceosome Activation in Fission Yeast

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It has recently become apparent that most introns are removed from pre-mRNA while the transcript is still engaged with RNA polymerase II (RNAPII). To gain insight into possible roles for chromatin in co-transcriptional splicing, we generated a genome-wide genetic interaction map in fission yeast and uncovered numerous connections between splicing and chromatin. The SWI/SNF remodeling complex is typically thought to activate gene expression by relieving barriers to polymerase elongation imposed by nucleosomes. Here we show that this remodeler is important for an early step in splicing in which Prp2, an RNA-dependent ATPase, is recruited to the assembling spliceosome to promote catalytic activation. Interestingly, introns with sub-optimal splice sites are particularly dependent on SWI/SNF, suggesting the impact of nucleosome dynamics on the kinetics of spliceosome assembly and catalysis. By monitoring nucleosome occupancy, we show significant alterations in nucleosome density in particular splicing and chromatin mutants, which generally paralleled the levels of RNAPII. Taken together, our findings challenge the notion that nucleosomes simply act as barriers to elongation; rather, we suggest that polymerase pausing at nucleosomes can activate gene expression by allowing more time for co-transcriptional splicing.

Vyšlo v časopise: Genetic Interaction Mapping Reveals a Role for the SWI/SNF Nucleosome Remodeler in Spliceosome Activation in Fission Yeast. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005074
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005074

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