A vertebrate RNA-binding protein Fox-1 regulates tissue-specific splicing via the pentanucleotide GCAUG.
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 (F1gamma) 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 F1gamma 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.
Jin
Yui
Y
Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma 630-0101, Japan.
Suzuki
Hitoshi
H
Maegawa
Shingo
S
Endo
Hitoshi
H
Sugano
Sumio
S
Hashimoto
Katsuyuki
K
Yasuda
Kunio
K
Inoue
Kunio
K
D000185:Actinin / Q000235:genetics; D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics; D066298:In Vitro Techniques; D051379:Mice; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000378:metabolism*; D009928:Organ Specificity; D012326:RNA Splicing; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; C117552:FOX-1 protein, C elegans; D005353:Fibronectins; D009841:Oligonucleotides; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; C465036:Rbfox1 protein, mouse; C472413:Rbfox1l protein, zebrafish; D029961:Zebrafish Proteins; D000185:Actinin