Tissue-specific splicing regulator Fox-1 induces exon skipping by interfering E complex formation on the downstream intron of human F1γ gene

Kazuhiro Fukumura, Ayako Kato, Yui Jin, Takashi Ideue, Tetsuro Hirose, Naoyuki Kataoka, Toshinobu Fujiwara, Hiroshi Sakamoto, Kunio Inoue

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Fox-1 is a regulator of tissue-specific splicing, via binding to the element (U)GCAUG in mRNA precursors, in muscles and neuronal cells. Fox-1 can regulate splicing positively or negatively, most likely depending on where it binds relative to the regulated exon. In cases where the (U)GCAUG element lies in an intron upstream of the alternative exon, Fox-1 protein functions as a splicing repressor to induce exon skipping. Here we report the mechanism of exon skipping regulated by Fox-1, using the hF1γ gene as a model system. We found that Fox-1 induces exon 9 skipping by repressing splicing of the downstream intron 9 via binding to the GCAUG repressor elements located in the upstream intron 8. In vitro splicing analyses showed that Fox-1 prevents formation of the pre-spliceosomal early (E) complex on intron 9. In addition, we located a region of the Fox-1 protein that is required for inducing exon skipping. Taken together, our data show a novel mechanism of how RNA-binding proteins regulate alternative splicing.

Original languageEnglish
Pages (from-to)5303-5311
Number of pages9
JournalNucleic Acids Research
Volume35
Issue number16
DOIs
Publication statusPublished - 01-08-2007

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Introns
Exons
Genes
RNA-Binding Proteins
RNA Precursors
Alternative Splicing
Muscle Cells
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Fukumura, Kazuhiro ; Kato, Ayako ; Jin, Yui ; Ideue, Takashi ; Hirose, Tetsuro ; Kataoka, Naoyuki ; Fujiwara, Toshinobu ; Sakamoto, Hiroshi ; Inoue, Kunio. / Tissue-specific splicing regulator Fox-1 induces exon skipping by interfering E complex formation on the downstream intron of human F1γ gene. In: Nucleic Acids Research. 2007 ; Vol. 35, No. 16. pp. 5303-5311.
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Tissue-specific splicing regulator Fox-1 induces exon skipping by interfering E complex formation on the downstream intron of human F1γ gene. / Fukumura, Kazuhiro; Kato, Ayako; Jin, Yui; Ideue, Takashi; Hirose, Tetsuro; Kataoka, Naoyuki; Fujiwara, Toshinobu; Sakamoto, Hiroshi; Inoue, Kunio.

In: Nucleic Acids Research, Vol. 35, No. 16, 01.08.2007, p. 5303-5311.

Research output: Contribution to journalArticle

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AU - Fukumura, Kazuhiro

AU - Kato, Ayako

AU - Jin, Yui

AU - Ideue, Takashi

AU - Hirose, Tetsuro

AU - Kataoka, Naoyuki

AU - Fujiwara, Toshinobu

AU - Sakamoto, Hiroshi

AU - Inoue, Kunio

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