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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...

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Autores principales: Nissen, Kelly E., Homer, Christina M., Ryan, Colm J., Shales, Michael, Krogan, Nevan J., Patrick, Kristin L., Guthrie, Christine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
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.
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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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