Cargando…

BEX1 is an RNA-dependent mediator of cardiomyopathy

Regulation of mRNA splicing, processing and stability is increasingly recognized as a critical control point in dynamically altering gene expression during stress or disease. Very little is understood of this process in heart failure. Here, we show that BEX1 is a heart failure-induced gene functioni...

Descripción completa

Detalles Bibliográficos
Autores principales: Accornero, Federica, Schips, Tobias G., Petrosino, Jennifer M., Gu, Shan-Qing, Kanisicak, Onur, van Berlo, Jop H., Molkentin, Jeffery D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709413/
https://www.ncbi.nlm.nih.gov/pubmed/29192139
http://dx.doi.org/10.1038/s41467-017-02005-1
_version_ 1783282771284721664
author Accornero, Federica
Schips, Tobias G.
Petrosino, Jennifer M.
Gu, Shan-Qing
Kanisicak, Onur
van Berlo, Jop H.
Molkentin, Jeffery D.
author_facet Accornero, Federica
Schips, Tobias G.
Petrosino, Jennifer M.
Gu, Shan-Qing
Kanisicak, Onur
van Berlo, Jop H.
Molkentin, Jeffery D.
author_sort Accornero, Federica
collection PubMed
description Regulation of mRNA splicing, processing and stability is increasingly recognized as a critical control point in dynamically altering gene expression during stress or disease. Very little is understood of this process in heart failure. Here, we show that BEX1 is a heart failure-induced gene functioning as an mRNA-associated protein that enhances expression of a subset of cardiac disease-promoting genes. Modeling the increase in BEX1 that occurs in disease, cardiac-specific BEX1 transgenic mice show worse cardiac disease with stress stimulation, whereas Bex1 gene-deleted mice are protected from heart failure-promoting insults. Proteomic and interactive screening assays show that BEX1 is part of a large ribonucleoprotein processing complex involved in regulating proinflammatory mRNA expression in the heart. Specifically, induction of BEX1 augments the stability and expression of AU-rich element containing mRNAs typically found within proinflammatory genes. Thus, BEX1 functions as an mRNA-dependent effector that augments pathology-promoting gene expression during heart failure.
format Online
Article
Text
id pubmed-5709413
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-57094132017-12-04 BEX1 is an RNA-dependent mediator of cardiomyopathy Accornero, Federica Schips, Tobias G. Petrosino, Jennifer M. Gu, Shan-Qing Kanisicak, Onur van Berlo, Jop H. Molkentin, Jeffery D. Nat Commun Article Regulation of mRNA splicing, processing and stability is increasingly recognized as a critical control point in dynamically altering gene expression during stress or disease. Very little is understood of this process in heart failure. Here, we show that BEX1 is a heart failure-induced gene functioning as an mRNA-associated protein that enhances expression of a subset of cardiac disease-promoting genes. Modeling the increase in BEX1 that occurs in disease, cardiac-specific BEX1 transgenic mice show worse cardiac disease with stress stimulation, whereas Bex1 gene-deleted mice are protected from heart failure-promoting insults. Proteomic and interactive screening assays show that BEX1 is part of a large ribonucleoprotein processing complex involved in regulating proinflammatory mRNA expression in the heart. Specifically, induction of BEX1 augments the stability and expression of AU-rich element containing mRNAs typically found within proinflammatory genes. Thus, BEX1 functions as an mRNA-dependent effector that augments pathology-promoting gene expression during heart failure. Nature Publishing Group UK 2017-11-30 /pmc/articles/PMC5709413/ /pubmed/29192139 http://dx.doi.org/10.1038/s41467-017-02005-1 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Accornero, Federica
Schips, Tobias G.
Petrosino, Jennifer M.
Gu, Shan-Qing
Kanisicak, Onur
van Berlo, Jop H.
Molkentin, Jeffery D.
BEX1 is an RNA-dependent mediator of cardiomyopathy
title BEX1 is an RNA-dependent mediator of cardiomyopathy
title_full BEX1 is an RNA-dependent mediator of cardiomyopathy
title_fullStr BEX1 is an RNA-dependent mediator of cardiomyopathy
title_full_unstemmed BEX1 is an RNA-dependent mediator of cardiomyopathy
title_short BEX1 is an RNA-dependent mediator of cardiomyopathy
title_sort bex1 is an rna-dependent mediator of cardiomyopathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709413/
https://www.ncbi.nlm.nih.gov/pubmed/29192139
http://dx.doi.org/10.1038/s41467-017-02005-1
work_keys_str_mv AT accornerofederica bex1isanrnadependentmediatorofcardiomyopathy
AT schipstobiasg bex1isanrnadependentmediatorofcardiomyopathy
AT petrosinojenniferm bex1isanrnadependentmediatorofcardiomyopathy
AT gushanqing bex1isanrnadependentmediatorofcardiomyopathy
AT kanisicakonur bex1isanrnadependentmediatorofcardiomyopathy
AT vanberlojoph bex1isanrnadependentmediatorofcardiomyopathy
AT molkentinjefferyd bex1isanrnadependentmediatorofcardiomyopathy