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Multiple decay events target HAC1 mRNA during splicing to regulate the unfolded protein response

In the unfolded protein response (UPR), stress in the endoplasmic reticulum (ER) activates a large transcriptional program to increase ER folding capacity. During the budding yeast UPR, Ire1 excises an intron from the HAC1 mRNA and the exon products of cleavage are ligated, and the translated protei...

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Detalles Bibliográficos
Autores principales: Cherry, Patrick D, Peach, Sally E, Hesselberth, Jay R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456296/
https://www.ncbi.nlm.nih.gov/pubmed/30874502
http://dx.doi.org/10.7554/eLife.42262
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author Cherry, Patrick D
Peach, Sally E
Hesselberth, Jay R
author_facet Cherry, Patrick D
Peach, Sally E
Hesselberth, Jay R
author_sort Cherry, Patrick D
collection PubMed
description In the unfolded protein response (UPR), stress in the endoplasmic reticulum (ER) activates a large transcriptional program to increase ER folding capacity. During the budding yeast UPR, Ire1 excises an intron from the HAC1 mRNA and the exon products of cleavage are ligated, and the translated protein induces hundreds of stress-response genes. Using cells with mutations in RNA repair and decay enzymes, we show that phosphorylation of two different HAC1 splicing intermediates is required for their degradation by the 5′→3′ exonuclease Xrn1 to enact opposing effects on the UPR. We also found that ligated but 2′-phosphorylated HAC1 mRNA is cleaved, yielding a decay intermediate with both 5′- and 2′-phosphates at its 5′-end that inhibit 5′→3′ decay and suggesting that Ire1 degrades incompletely processed HAC1. These decay events expand the scope of RNA-based regulation in the budding yeast UPR and have implications for the control of the metazoan UPR.
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spelling pubmed-64562962019-04-10 Multiple decay events target HAC1 mRNA during splicing to regulate the unfolded protein response Cherry, Patrick D Peach, Sally E Hesselberth, Jay R eLife Chromosomes and Gene Expression In the unfolded protein response (UPR), stress in the endoplasmic reticulum (ER) activates a large transcriptional program to increase ER folding capacity. During the budding yeast UPR, Ire1 excises an intron from the HAC1 mRNA and the exon products of cleavage are ligated, and the translated protein induces hundreds of stress-response genes. Using cells with mutations in RNA repair and decay enzymes, we show that phosphorylation of two different HAC1 splicing intermediates is required for their degradation by the 5′→3′ exonuclease Xrn1 to enact opposing effects on the UPR. We also found that ligated but 2′-phosphorylated HAC1 mRNA is cleaved, yielding a decay intermediate with both 5′- and 2′-phosphates at its 5′-end that inhibit 5′→3′ decay and suggesting that Ire1 degrades incompletely processed HAC1. These decay events expand the scope of RNA-based regulation in the budding yeast UPR and have implications for the control of the metazoan UPR. eLife Sciences Publications, Ltd 2019-03-15 /pmc/articles/PMC6456296/ /pubmed/30874502 http://dx.doi.org/10.7554/eLife.42262 Text en © 2019, Cherry et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Chromosomes and Gene Expression
Cherry, Patrick D
Peach, Sally E
Hesselberth, Jay R
Multiple decay events target HAC1 mRNA during splicing to regulate the unfolded protein response
title Multiple decay events target HAC1 mRNA during splicing to regulate the unfolded protein response
title_full Multiple decay events target HAC1 mRNA during splicing to regulate the unfolded protein response
title_fullStr Multiple decay events target HAC1 mRNA during splicing to regulate the unfolded protein response
title_full_unstemmed Multiple decay events target HAC1 mRNA during splicing to regulate the unfolded protein response
title_short Multiple decay events target HAC1 mRNA during splicing to regulate the unfolded protein response
title_sort multiple decay events target hac1 mrna during splicing to regulate the unfolded protein response
topic Chromosomes and Gene Expression
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456296/
https://www.ncbi.nlm.nih.gov/pubmed/30874502
http://dx.doi.org/10.7554/eLife.42262
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