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

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

Author information

1
Department of Medicine III, University of Heidelberg, D-69120 Heidelberg, Germany German Centre for Cardiovascular Research (DZHK), partner site Heidelberg/Mannheim, D-69120 Heidelberg, Germany.
2
Chair for Clinical Bioinformatics, Saarland University, D-66123 Saarbrücken, Germany Department of Human Genetics, Saarland University, D-66123 Saarbrücken, Germany.
3
Department of Medicine II, University of Ulm, D-89081 Ulm, Germany.
4
Department of Human Genetics, Saarland University, D-66123 Saarbrücken, Germany.
5
Comprehensive Biomarker Center, D-69120 Heidelberg, Germany.
6
Department of Medicine III, University of Heidelberg, D-69120 Heidelberg, Germany.
7
EMBL, European Molecular Biology Laboratory, Genomics Core Facility, D-69117 Heidelberg, Germany.
8
Department of Medicine II, University of Ulm, D-89081 Ulm, Germany wolfgang.rottbauer@uniklinik-ulm.de.

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

PMID:
26116573
PMCID:
PMC4541041
DOI:
10.1242/jcs.166850
[Indexed for MEDLINE]
Free PMC Article

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