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

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...

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Bibliographic Details
Main Authors: Frese, Karen S. (Author) , Meder, Benjamin (Author) , Haas, Jan (Author) , Heilmeier, Britta (Author) , Fischer, Simon (Author) , Köhler, Doreen (Author) , Katus, Hugo (Author)
Format: Article (Journal)
Language:English
Published: 2015
In: Journal of cell science
Year: 2015, Volume: 128, Issue: 16, Pages: 3030-3040
ISSN:1477-9137
DOI:10.1242/jcs.166850
Online Access:Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1242/jcs.166850
Verlag, kostenfrei, Volltext: http://jcs.biologists.org/content/joces/128/16/3030
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Author Notes:Karen S. Frese, Benjamin Meder, Andreas Keller, Steffen Just, Jan Haas, Britta Vogel, Simon Fischer, Christina Backes, Mark Matzas, Doreen Köhler, Vladimir Benes, Hugo A. Katus and Wolfgang Rottbauer

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520 |a 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. 
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