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ARGLU1 is a transcriptional coactivator and splicing regulator important for stress hormone signaling and development

Stress hormones bind and activate the glucocorticoid receptor (GR) in many tissues including the brain. We identified arginine and glutamate rich 1 (ARGLU1) in a screen for new modulators of glucocorticoid signaling in the CNS. Biochemical studies show that the glutamate rich C-terminus of ARGLU1 co...

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Autores principales: Magomedova, Lilia, Tiefenbach, Jens, Zilberman, Emma, Le Billan, Florian, Voisin, Veronique, Saikali, Michael, Boivin, Vincent, Robitaille, Melanie, Gueroussov, Serge, Irimia, Manuel, Ray, Debashish, Patel, Rucha, Xu, ChangJiang, Jeyasuria, Pancharatnam, Bader, Gary D, Hughes, Timothy R, Morris, Quaid D, Scott, Michelle S, Krause, Henry, Angers, Stephane, Blencowe, Benjamin J, Cummins, Carolyn L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451108/
https://www.ncbi.nlm.nih.gov/pubmed/30698747
http://dx.doi.org/10.1093/nar/gkz010
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author Magomedova, Lilia
Tiefenbach, Jens
Zilberman, Emma
Le Billan, Florian
Voisin, Veronique
Saikali, Michael
Boivin, Vincent
Robitaille, Melanie
Gueroussov, Serge
Irimia, Manuel
Ray, Debashish
Patel, Rucha
Xu, ChangJiang
Jeyasuria, Pancharatnam
Bader, Gary D
Hughes, Timothy R
Morris, Quaid D
Scott, Michelle S
Krause, Henry
Angers, Stephane
Blencowe, Benjamin J
Cummins, Carolyn L
author_facet Magomedova, Lilia
Tiefenbach, Jens
Zilberman, Emma
Le Billan, Florian
Voisin, Veronique
Saikali, Michael
Boivin, Vincent
Robitaille, Melanie
Gueroussov, Serge
Irimia, Manuel
Ray, Debashish
Patel, Rucha
Xu, ChangJiang
Jeyasuria, Pancharatnam
Bader, Gary D
Hughes, Timothy R
Morris, Quaid D
Scott, Michelle S
Krause, Henry
Angers, Stephane
Blencowe, Benjamin J
Cummins, Carolyn L
author_sort Magomedova, Lilia
collection PubMed
description Stress hormones bind and activate the glucocorticoid receptor (GR) in many tissues including the brain. We identified arginine and glutamate rich 1 (ARGLU1) in a screen for new modulators of glucocorticoid signaling in the CNS. Biochemical studies show that the glutamate rich C-terminus of ARGLU1 coactivates multiple nuclear receptors including the glucocorticoid receptor (GR) and the arginine rich N-terminus interacts with splicing factors and binds to RNA. RNA-seq of neural cells depleted of ARGLU1 revealed significant changes in the expression and alternative splicing of distinct genes involved in neurogenesis. Loss of ARGLU1 is embryonic lethal in mice, and knockdown in zebrafish causes neurodevelopmental and heart defects. Treatment with dexamethasone, a GR activator, also induces changes in the pattern of alternatively spliced genes, many of which were lost when ARGLU1 was absent. Importantly, the genes found to be alternatively spliced in response to glucocorticoid treatment were distinct from those under transcriptional control by GR, suggesting an additional mechanism of glucocorticoid action is present in neural cells. Our results thus show that ARGLU1 is a novel factor for embryonic development that modulates basal transcription and alternative splicing in neural cells with consequences for glucocorticoid signaling.
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spelling pubmed-64511082019-04-09 ARGLU1 is a transcriptional coactivator and splicing regulator important for stress hormone signaling and development Magomedova, Lilia Tiefenbach, Jens Zilberman, Emma Le Billan, Florian Voisin, Veronique Saikali, Michael Boivin, Vincent Robitaille, Melanie Gueroussov, Serge Irimia, Manuel Ray, Debashish Patel, Rucha Xu, ChangJiang Jeyasuria, Pancharatnam Bader, Gary D Hughes, Timothy R Morris, Quaid D Scott, Michelle S Krause, Henry Angers, Stephane Blencowe, Benjamin J Cummins, Carolyn L Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Stress hormones bind and activate the glucocorticoid receptor (GR) in many tissues including the brain. We identified arginine and glutamate rich 1 (ARGLU1) in a screen for new modulators of glucocorticoid signaling in the CNS. Biochemical studies show that the glutamate rich C-terminus of ARGLU1 coactivates multiple nuclear receptors including the glucocorticoid receptor (GR) and the arginine rich N-terminus interacts with splicing factors and binds to RNA. RNA-seq of neural cells depleted of ARGLU1 revealed significant changes in the expression and alternative splicing of distinct genes involved in neurogenesis. Loss of ARGLU1 is embryonic lethal in mice, and knockdown in zebrafish causes neurodevelopmental and heart defects. Treatment with dexamethasone, a GR activator, also induces changes in the pattern of alternatively spliced genes, many of which were lost when ARGLU1 was absent. Importantly, the genes found to be alternatively spliced in response to glucocorticoid treatment were distinct from those under transcriptional control by GR, suggesting an additional mechanism of glucocorticoid action is present in neural cells. Our results thus show that ARGLU1 is a novel factor for embryonic development that modulates basal transcription and alternative splicing in neural cells with consequences for glucocorticoid signaling. Oxford University Press 2019-04-08 2019-01-30 /pmc/articles/PMC6451108/ /pubmed/30698747 http://dx.doi.org/10.1093/nar/gkz010 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Gene regulation, Chromatin and Epigenetics
Magomedova, Lilia
Tiefenbach, Jens
Zilberman, Emma
Le Billan, Florian
Voisin, Veronique
Saikali, Michael
Boivin, Vincent
Robitaille, Melanie
Gueroussov, Serge
Irimia, Manuel
Ray, Debashish
Patel, Rucha
Xu, ChangJiang
Jeyasuria, Pancharatnam
Bader, Gary D
Hughes, Timothy R
Morris, Quaid D
Scott, Michelle S
Krause, Henry
Angers, Stephane
Blencowe, Benjamin J
Cummins, Carolyn L
ARGLU1 is a transcriptional coactivator and splicing regulator important for stress hormone signaling and development
title ARGLU1 is a transcriptional coactivator and splicing regulator important for stress hormone signaling and development
title_full ARGLU1 is a transcriptional coactivator and splicing regulator important for stress hormone signaling and development
title_fullStr ARGLU1 is a transcriptional coactivator and splicing regulator important for stress hormone signaling and development
title_full_unstemmed ARGLU1 is a transcriptional coactivator and splicing regulator important for stress hormone signaling and development
title_short ARGLU1 is a transcriptional coactivator and splicing regulator important for stress hormone signaling and development
title_sort arglu1 is a transcriptional coactivator and splicing regulator important for stress hormone signaling and development
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451108/
https://www.ncbi.nlm.nih.gov/pubmed/30698747
http://dx.doi.org/10.1093/nar/gkz010
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