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BEX1 is an RNA-dependent mediator of cardiomyopathy

Author

Listed:
  • Federica Accornero

    (Cincinnati Children’s Hospital Medical Center
    Dorothy M. Davis Heart and Lung Research Institute, Department of Physiology and Cell Biology, Ohio State University)

  • Tobias G. Schips

    (Cincinnati Children’s Hospital Medical Center)

  • Jennifer M. Petrosino

    (Dorothy M. Davis Heart and Lung Research Institute, Department of Physiology and Cell Biology, Ohio State University)

  • Shan-Qing Gu

    (Dorothy M. Davis Heart and Lung Research Institute, Department of Physiology and Cell Biology, Ohio State University)

  • Onur Kanisicak

    (Cincinnati Children’s Hospital Medical Center)

  • Jop H. Berlo

    (Cincinnati Children’s Hospital Medical Center
    Lillehei Heart Institute, University of Minnesota)

  • Jeffery D. Molkentin

    (Cincinnati Children’s Hospital Medical Center
    Howard Hughes Medical Institute)

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.

Suggested Citation

  • Federica Accornero & Tobias G. Schips & Jennifer M. Petrosino & Shan-Qing Gu & Onur Kanisicak & Jop H. Berlo & Jeffery D. Molkentin, 2017. "BEX1 is an RNA-dependent mediator of cardiomyopathy," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02005-1
    DOI: 10.1038/s41467-017-02005-1
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    Cited by:

    1. Christopher J. Gilbert & Charles P. Rabolli & Volha A. Golubeva & Kristina M. Sattler & Meifang Wang & Arsh Ketabforoush & W. David Arnold & Christoph Lepper & Federica Accornero, 2024. "YTHDF2 governs muscle size through a targeted modulation of proteostasis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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