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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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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 |
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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 |
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