RNA splicing regulated by RBFOX1 is essential for cardiac function in zebrafish

J Cell Sci. 2015 Aug 15;128(16):3030-40. doi: 10.1242/jcs.166850. Epub 2015 Jun 26.

Abstract

Alternative splicing is one of the major mechanisms through which the proteomic and functional diversity of eukaryotes is achieved. However, the complex nature of the splicing machinery, its associated splicing regulators and the functional implications of alternatively spliced transcripts are only poorly understood. Here, we investigated the functional role of the splicing regulator rbfox1 in vivo using the zebrafish as a model system. We found that loss of rbfox1 led to progressive cardiac contractile dysfunction and heart failure. By using deep-transcriptome sequencing and quantitative real-time PCR, we show that depletion of rbfox1 in zebrafish results in an altered isoform expression of several crucial target genes, such as actn3a and hug. This study underlines that tightly regulated splicing is necessary for unconstrained cardiac function and renders the splicing regulator rbfox1 an interesting target for investigation in human heart failure and cardiomyopathy.

Keywords: Deep sequencing; Dilated cardiomyopathy; Genetics; Splicing; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinin / genetics
  • Actinin / metabolism
  • Alternative Splicing / genetics*
  • Animals
  • Cardiomyopathies / genetics*
  • Cardiomyopathies / pathology
  • Heart Failure / genetics*
  • Heart Failure / physiopathology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Neuropeptides / genetics
  • RNA Splicing Factors
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / genetics
  • Transcriptome / genetics*
  • Zebrafish / genetics

Substances

  • Neuropeptides
  • RBFOX1 protein, human
  • RNA Splicing Factors
  • RNA-Binding Proteins
  • Actinin