ZFIN ID: ZDB-PUB-030715-9
A vertebrate RNA-binding protein Fox-1 regulates tissue-specific splicing via the pentanucleotide GCAUG
Jin, Y., Suzuki, H., Maegawa, S., Endo, H., Sugano, S., Hashimoto, K., Yasuda, K., and Inoue, K.
Date: 2003
Source: The EMBO journal   22(4): 905-912 (Journal)
Registered Authors: Inoue, Kunio, Jin, Yui, Maegawa, Shingo
Keywords: alternative splicing/Fox-1/GCAUG/RNA binding
MeSH Terms:
  • Actinin/genetics
  • Animals
  • Caenorhabditis elegans Proteins/genetics*
  • Caenorhabditis elegans Proteins/metabolism*
  • Fibronectins/genetics
  • In Vitro Techniques
  • Mice
  • Molecular Sequence Data
  • Oligonucleotides/metabolism*
  • Organ Specificity
  • RNA Splicing*
  • RNA-Binding Proteins/genetics*
  • RNA-Binding Proteins/metabolism*
  • Zebrafish/genetics
  • Zebrafish/physiology
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism*
PubMed: 12574126 Full text @ EMBO J.
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ABSTRACT
Alternative splicing is one of the central mechanisms that regulate eukaryotic gene expression. Here we report a tissue-specific RNA-binding protein, Fox-1, which regulates alternative splicing in vertebrates. Fox-1 bound specifically to a pentanucleotide GCAUG in vitro. In zebrafish and mouse, fox-1 is expressed in heart and skeletal muscles. As candidates for muscle-specific targets of Fox-1, we considered two genes, the human mitochondrial ATP synthase {gamma}-subunit gene (F1{gamma}) and the rat {alpha}-actinin gene, because their primary transcripts contain several copies of GCAUG. In transfection experiments, Fox-1 induced muscle-specific exon skipping of the F1{gamma} gene via binding to GCAUG sequences upstream of the regulated exon. Fox-1 also regulated mutually exclusive splicing of the {alpha}-actinin gene, antagonizing the repressive effect of polypyrimidine tract-binding protein (PTB). It has been reported that GCAUG is essential for the alternative splicing regulation of several genes including fibronectin. We found that Fox-1 promoted inclusion of the fibronectin EIIIB exon. Thus, we conclude that Fox-1 plays key roles in both positive and negative regulation of tissue-specific splicing via GCAUG.
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