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The differential expression of alternatively polyadenylated transcripts is a common stress-induced response mechanism that modulates mammalian mRNA expression in a quantitative and qualitative fashion

Stress adaptation plays a pivotal role in biological processes and requires tight regulation of gene expression. In this study, we explored the effect of cellular stress on mRNA polyadenylation and investigated the implications of regulated polyadenylation site usage on mammalian gene expression. Hi...

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Autores principales: Hollerer, Ina, Curk, Tomaz, Haase, Bettina, Benes, Vladimir, Hauer, Christian, Neu-Yilik, Gabriele, Bhuvanagiri, Madhuri, Hentze, Matthias W., Kulozik, Andreas E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4986898/
https://www.ncbi.nlm.nih.gov/pubmed/27407180
http://dx.doi.org/10.1261/rna.055657.115
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author Hollerer, Ina
Curk, Tomaz
Haase, Bettina
Benes, Vladimir
Hauer, Christian
Neu-Yilik, Gabriele
Bhuvanagiri, Madhuri
Hentze, Matthias W.
Kulozik, Andreas E.
author_facet Hollerer, Ina
Curk, Tomaz
Haase, Bettina
Benes, Vladimir
Hauer, Christian
Neu-Yilik, Gabriele
Bhuvanagiri, Madhuri
Hentze, Matthias W.
Kulozik, Andreas E.
author_sort Hollerer, Ina
collection PubMed
description Stress adaptation plays a pivotal role in biological processes and requires tight regulation of gene expression. In this study, we explored the effect of cellular stress on mRNA polyadenylation and investigated the implications of regulated polyadenylation site usage on mammalian gene expression. High-confidence polyadenylation site mapping combined with global pre-mRNA and mRNA expression profiling revealed that stress induces an accumulation of genes with differentially expressed polyadenylated mRNA isoforms in human cells. Specifically, stress provokes a global trend in polyadenylation site usage toward decreased utilization of promoter-proximal poly(A) sites in introns or ORFs and increased utilization of promoter-distal polyadenylation sites in intergenic regions. This extensively affects gene expression beyond regulating mRNA abundance by changing mRNA length and by altering the configuration of open reading frames. Our study highlights the impact of post-transcriptional mechanisms on stress-dependent gene regulation and reveals the differential expression of alternatively polyadenylated transcripts as a common stress-induced mechanism in mammalian cells.
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spelling pubmed-49868982016-09-01 The differential expression of alternatively polyadenylated transcripts is a common stress-induced response mechanism that modulates mammalian mRNA expression in a quantitative and qualitative fashion Hollerer, Ina Curk, Tomaz Haase, Bettina Benes, Vladimir Hauer, Christian Neu-Yilik, Gabriele Bhuvanagiri, Madhuri Hentze, Matthias W. Kulozik, Andreas E. RNA Article Stress adaptation plays a pivotal role in biological processes and requires tight regulation of gene expression. In this study, we explored the effect of cellular stress on mRNA polyadenylation and investigated the implications of regulated polyadenylation site usage on mammalian gene expression. High-confidence polyadenylation site mapping combined with global pre-mRNA and mRNA expression profiling revealed that stress induces an accumulation of genes with differentially expressed polyadenylated mRNA isoforms in human cells. Specifically, stress provokes a global trend in polyadenylation site usage toward decreased utilization of promoter-proximal poly(A) sites in introns or ORFs and increased utilization of promoter-distal polyadenylation sites in intergenic regions. This extensively affects gene expression beyond regulating mRNA abundance by changing mRNA length and by altering the configuration of open reading frames. Our study highlights the impact of post-transcriptional mechanisms on stress-dependent gene regulation and reveals the differential expression of alternatively polyadenylated transcripts as a common stress-induced mechanism in mammalian cells. Cold Spring Harbor Laboratory Press 2016-09 /pmc/articles/PMC4986898/ /pubmed/27407180 http://dx.doi.org/10.1261/rna.055657.115 Text en © 2016 Hollerer et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by/4.0/ This article, published in RNA, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hollerer, Ina
Curk, Tomaz
Haase, Bettina
Benes, Vladimir
Hauer, Christian
Neu-Yilik, Gabriele
Bhuvanagiri, Madhuri
Hentze, Matthias W.
Kulozik, Andreas E.
The differential expression of alternatively polyadenylated transcripts is a common stress-induced response mechanism that modulates mammalian mRNA expression in a quantitative and qualitative fashion
title The differential expression of alternatively polyadenylated transcripts is a common stress-induced response mechanism that modulates mammalian mRNA expression in a quantitative and qualitative fashion
title_full The differential expression of alternatively polyadenylated transcripts is a common stress-induced response mechanism that modulates mammalian mRNA expression in a quantitative and qualitative fashion
title_fullStr The differential expression of alternatively polyadenylated transcripts is a common stress-induced response mechanism that modulates mammalian mRNA expression in a quantitative and qualitative fashion
title_full_unstemmed The differential expression of alternatively polyadenylated transcripts is a common stress-induced response mechanism that modulates mammalian mRNA expression in a quantitative and qualitative fashion
title_short The differential expression of alternatively polyadenylated transcripts is a common stress-induced response mechanism that modulates mammalian mRNA expression in a quantitative and qualitative fashion
title_sort differential expression of alternatively polyadenylated transcripts is a common stress-induced response mechanism that modulates mammalian mrna expression in a quantitative and qualitative fashion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4986898/
https://www.ncbi.nlm.nih.gov/pubmed/27407180
http://dx.doi.org/10.1261/rna.055657.115
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