BEX1 is an RNA-dependent mediator of cardiomyopathy

Nat Commun. 2017 Nov 30;8(1):1875. doi: 10.1038/s41467-017-02005-1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomegaly / genetics*
  • Cardiomegaly / metabolism
  • Cardiomyopathies / genetics*
  • Cardiomyopathies / metabolism
  • Case-Control Studies
  • Gene Expression Regulation*
  • Heart Failure / genetics*
  • Heart Failure / metabolism
  • Humans
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Protein Interaction Mapping
  • RNA Splicing
  • RNA, Messenger / metabolism*
  • Rats

Substances

  • BEX1 protein, human
  • Bex1 protein, mouse
  • Nerve Tissue Proteins
  • RNA, Messenger