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Genes Dev. 2017 Apr 1;31(7):688-701. doi: 10.1101/gad.295287.116.

The histone variant H2A.Z promotes splicing of weak introns.

Author information

1
Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco 94158, California, USA.
2
Systems Biology Ireland, University College Dublin, Belfield, Dublin 4, Ireland.
3
Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco 94158, California, USA.
4
California Institute for Quantitative Biosciences (QB3), San Francisco 94158, California, USA.
5
J. David Gladstone Institutes, San Francisco 94158, California, USA.
6
Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, Texas 77807, USA.

Abstract

Multiple lines of evidence implicate chromatin in the regulation of premessenger RNA (pre-mRNA) splicing. However, the influence of chromatin factors on cotranscriptional splice site usage remains unclear. Here we investigated the function of the highly conserved histone variant H2A.Z in pre-mRNA splicing using the intron-rich model yeast Schizosaccharomyces pombe Using epistatic miniarray profiles (EMAPs) to survey the genetic interaction landscape of the Swr1 nucleosome remodeling complex, which deposits H2A.Z, we uncovered evidence for functional interactions with components of the spliceosome. In support of these genetic connections, splicing-specific microarrays show that H2A.Z and the Swr1 ATPase are required during temperature stress for the efficient splicing of a subset of introns. Notably, affected introns are enriched for H2A.Z occupancy and more likely to contain nonconsensus splice sites. To test the significance of the latter correlation, we mutated the splice sites in an affected intron to consensus and found that this suppressed the requirement for H2A.Z in splicing of that intron. These data suggest that H2A.Z occupancy promotes cotranscriptional splicing of suboptimal introns that may otherwise be discarded via proofreading ATPases. Consistent with this model, we show that overexpression of splicing ATPase Prp16 suppresses both the growth and splicing defects seen in the absence of H2A.Z.

KEYWORDS:

H2A.Z; Prp16; Swr1 complex; chromatin; fission yeast; pre-mRNA splicing

PMID:
28446597
PMCID:
PMC5411709
DOI:
10.1101/gad.295287.116
[Indexed for MEDLINE]
Free PMC Article

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