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RBFox1-mediated RNA splicing regulates cardiac hypertrophy and heart failure.

Publication ,  Journal Article
Gao, C; Ren, S; Lee, J-H; Qiu, J; Chapski, DJ; Rau, CD; Zhou, Y; Abdellatif, M; Nakano, A; Vondriska, TM; Xiao, X; Fu, X-D; Chen, J-N; Wang, Y
Published in: J Clin Invest
January 2016

RNA splicing is a major contributor to total transcriptome complexity; however, the functional role and regulation of splicing in heart failure remain poorly understood. Here, we used a total transcriptome profiling and bioinformatic analysis approach and identified a muscle-specific isoform of an RNA splicing regulator, RBFox1 (also known as A2BP1), as a prominent regulator of alternative RNA splicing during heart failure. Evaluation of developing murine and zebrafish hearts revealed that RBFox1 is induced during postnatal cardiac maturation. However, we found that RBFox1 is markedly diminished in failing human and mouse hearts. In a mouse model, RBFox1 deficiency in the heart promoted pressure overload-induced heart failure. We determined that RBFox1 is a potent regulator of RNA splicing and is required for a conserved splicing process of transcription factor MEF2 family members that yields different MEF2 isoforms with differential effects on cardiac hypertrophic gene expression. Finally, induction of RBFox1 expression in murine pressure overload models substantially attenuated cardiac hypertrophy and pathological manifestations. Together, this study identifies regulation of RNA splicing by RBFox1 as an important player in transcriptome reprogramming during heart failure that influence pathogenesis of the disease.

Duke Scholars

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

January 2016

Volume

126

Issue

1

Start / End Page

195 / 206

Location

United States

Related Subject Headings

  • Transcriptome
  • RNA-Binding Proteins
  • RNA Splicing Factors
  • RNA Splicing
  • Mice
  • MEF2 Transcription Factors
  • Immunology
  • Humans
  • Heart Failure
  • Cardiomegaly
 

Citation

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MLA
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Gao, C., Ren, S., Lee, J.-H., Qiu, J., Chapski, D. J., Rau, C. D., … Wang, Y. (2016). RBFox1-mediated RNA splicing regulates cardiac hypertrophy and heart failure. J Clin Invest, 126(1), 195–206. https://doi.org/10.1172/JCI84015
Gao, Chen, Shuxun Ren, Jae-Hyung Lee, Jinsong Qiu, Douglas J. Chapski, Christoph D. Rau, Yu Zhou, et al. “RBFox1-mediated RNA splicing regulates cardiac hypertrophy and heart failure.J Clin Invest 126, no. 1 (January 2016): 195–206. https://doi.org/10.1172/JCI84015.
Gao C, Ren S, Lee J-H, Qiu J, Chapski DJ, Rau CD, et al. RBFox1-mediated RNA splicing regulates cardiac hypertrophy and heart failure. J Clin Invest. 2016 Jan;126(1):195–206.
Gao, Chen, et al. “RBFox1-mediated RNA splicing regulates cardiac hypertrophy and heart failure.J Clin Invest, vol. 126, no. 1, Jan. 2016, pp. 195–206. Pubmed, doi:10.1172/JCI84015.
Gao C, Ren S, Lee J-H, Qiu J, Chapski DJ, Rau CD, Zhou Y, Abdellatif M, Nakano A, Vondriska TM, Xiao X, Fu X-D, Chen J-N, Wang Y. RBFox1-mediated RNA splicing regulates cardiac hypertrophy and heart failure. J Clin Invest. 2016 Jan;126(1):195–206.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

January 2016

Volume

126

Issue

1

Start / End Page

195 / 206

Location

United States

Related Subject Headings

  • Transcriptome
  • RNA-Binding Proteins
  • RNA Splicing Factors
  • RNA Splicing
  • Mice
  • MEF2 Transcription Factors
  • Immunology
  • Humans
  • Heart Failure
  • Cardiomegaly