PUBLICATION

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

Authors
Frese, K.S., Meder, B., Keller, A., Just, S., Haas, J., Vogel, B., Fischer, S., Backes, C., Matzas, M., Köhler, D., Benes, V., Katus, H.A., Rottbauer, W.
ID
ZDB-PUB-150628-2
Date
2015
Source
Journal of Cell Science   128(16): 3030-40 (Journal)
Registered Authors
Fischer, Simon, Frese, Karen, Just, Steffen, Meder, Benjamin, Rottbauer, Wolfgang, Vogel, Britta
Keywords
Dilated cardiomyopathy, Genetics, Zebrafish, Deep sequencing, Splicing
MeSH Terms
  • Heart Failure/genetics*
  • Heart Failure/physiopathology
  • RNA-Binding Proteins/biosynthesis
  • RNA-Binding Proteins/genetics
  • Animals
  • Zebrafish/genetics
  • Alternative Splicing/genetics*
  • Actinin/genetics
  • Actinin/metabolism
  • High-Throughput Nucleotide Sequencing
  • RNA Splicing Factors
  • Cardiomyopathies/genetics*
  • Cardiomyopathies/pathology
  • Neuropeptides/genetics
  • Humans
  • Transcriptome/genetics*
(all 16)
PubMed
26116573 Full text @ J. Cell Sci.
Abstract
Alternative splicing (AS) is one of the major mechanisms to warrant the proteomic and functional diversity of eukaryotes. However, the complex nature of the splicing machinery, its associated splicing regulators and the functional implications of alternatively spliced transcripts is only poorly understood.We investigated here the functional role of the splicing regulator rbfox1 in vivo using the zebrafish as a model system. We find that loss-of rbfox1 leads 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 to be investigated in human heart failure and cardiomyopathy.
Genes / Markers
Figures
Figure Gallery (4 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
f1TgTransgenic Insertion
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    actn3aMO1-actn3aMRPHLNO
    camk2g1MO2-camk2g1MRPHLNO
    elavl1bMO1-elavl1bMRPHLNO
    hacd2MO1-hacd2MRPHLNO
    ktn1MO1-ktn1MRPHLNO
    rbfox1MO3-rbfox1MRPHLNO
    rbfox1MO4-rbfox1MRPHLNO
    1 - 7 of 7
    Show
    Fish
    Antibodies
    Orthology
    No data available
    Engineered Foreign Genes
    Marker Marker Type Name
    GFPEFGGFP
    1 - 1 of 1
    Show
    Mapping
    No data available