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  • The EMBO Journal (2003) 22, 905 - 912
  • doi:10.1093/emboj/cdg089

  • Subject Category:

A vertebrate RNA-binding protein Fox-1 regulates tissue-specific splicing via the pentanucleotide GCAUG

Yui Jin1, Hitoshi Suzuki2, Shingo Maegawa3, Hitoshi Endo4, Sumio Sugano5, Katsuyuki Hashimoto6, Kunio Yasuda1 and Kunio Inoue1

  1. Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma 630-0101, USA
  2. Present address: Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, FL 33136, USA
  3. Present address: Department of Biology, University of Pennsylvania, PA 19104, USA
  4. Department of Biochemistry, Jichi Medical School, Tochigi 329-0498, Japan
  5. The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639 Japan
  6. Division of Genetic Resources, National Institute of Infectious Diseases, Tokyo 162-8640, Japan

Correspondence to:

Kunio Inoue, E-mail: kunio@bs.aist-nara.ac.jp

Received 23 September 2002; Accepted 20 December 2002; Revised 19 December 2002

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.

  • Keywords:

    • alternative splicing,
    • Fox-1,
    • GCAUG,
    • RNA binding