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The histone variant H2A.Z promotes splicing of weak introns
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 sp...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411709/ https://www.ncbi.nlm.nih.gov/pubmed/28446597 http://dx.doi.org/10.1101/gad.295287.116 |
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author | Nissen, Kelly E. Homer, Christina M. Ryan, Colm J. Shales, Michael Krogan, Nevan J. Patrick, Kristin L. Guthrie, Christine |
author_facet | Nissen, Kelly E. Homer, Christina M. Ryan, Colm J. Shales, Michael Krogan, Nevan J. Patrick, Kristin L. Guthrie, Christine |
author_sort | Nissen, Kelly E. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5411709 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-54117092017-10-01 The histone variant H2A.Z promotes splicing of weak introns Nissen, Kelly E. Homer, Christina M. Ryan, Colm J. Shales, Michael Krogan, Nevan J. Patrick, Kristin L. Guthrie, Christine Genes Dev Research Paper 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. Cold Spring Harbor Laboratory Press 2017-04-01 /pmc/articles/PMC5411709/ /pubmed/28446597 http://dx.doi.org/10.1101/gad.295287.116 Text en © 2017 Nissen et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Research Paper Nissen, Kelly E. Homer, Christina M. Ryan, Colm J. Shales, Michael Krogan, Nevan J. Patrick, Kristin L. Guthrie, Christine The histone variant H2A.Z promotes splicing of weak introns |
title | The histone variant H2A.Z promotes splicing of weak introns |
title_full | The histone variant H2A.Z promotes splicing of weak introns |
title_fullStr | The histone variant H2A.Z promotes splicing of weak introns |
title_full_unstemmed | The histone variant H2A.Z promotes splicing of weak introns |
title_short | The histone variant H2A.Z promotes splicing of weak introns |
title_sort | histone variant h2a.z promotes splicing of weak introns |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411709/ https://www.ncbi.nlm.nih.gov/pubmed/28446597 http://dx.doi.org/10.1101/gad.295287.116 |
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