BEX1 is an RNA-dependent mediator of cardiomyopathy

Federica Accornero, Tobias G. Schips, Jennifer M. Petrosino, Shan Qing Gu, Onur Kanisicak, Jop H. Van Berlo, Jeffery D. Molkentin

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number1875
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

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    Accornero, F., Schips, T. G., Petrosino, J. M., Gu, S. Q., Kanisicak, O., Van Berlo, J. H., & Molkentin, J. D. (2017). BEX1 is an RNA-dependent mediator of cardiomyopathy. Nature communications, 8(1), [1875]. https://doi.org/10.1038/s41467-017-02005-1