PUBLICATION
A vertebrate RNA-binding protein Fox-1 regulates tissue-specific splicing via the pentanucleotide GCAUG
- Authors
- Jin, Y., Suzuki, H., Maegawa, S., Endo, H., Sugano, S., Hashimoto, K., Yasuda, K., and Inoue, K.
- ID
- ZDB-PUB-030715-9
- 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.
Citation
Jin, Y., Suzuki, H., Maegawa, S., Endo, H., Sugano, S., Hashimoto, K., Yasuda, K., and Inoue, K. (2003) A vertebrate RNA-binding protein Fox-1 regulates tissue-specific splicing via the pentanucleotide GCAUG. The EMBO journal. 22(4):905-912.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping