Tissue-specific Splicing Regulator Fox-1 Induces Exon Skipping by Interfering E Complex Formation on the Downstream Intron of Human F1gamma Gene

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2007 Aug 10

PMID 17686786

Citations 23

Authors

Kazuhiro Fukumura

Ayako Kato

Yui Jin

Takashi Ideue

Tetsuro Hirose

Naoyuki Kataoka

Toshinobu Fujiwara

Hiroshi Sakamoto

Kunio Inoue

Affiliations

Soon will be listed here.

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 hF1gamma 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.

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