TY - JOUR
T1 - Tissue-specific splicing regulator Fox-1 induces exon skipping by interfering E complex formation on the downstream intron of human F1γ gene
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
N1 - Funding Information:
We thank E. Sakashita for valuable advice on the in vitro splicing system, T. Tani, A. Mayeda and Y. Mishima for critical comments on the manuscript. This work was supported by Grant-in-Aids for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan, and in part by the Mitsubishi Foundation, the Hyogo Foundation and the Naito Foundation. Funding to pay the Open Access publication charges for this article was provided by JSPS.
PY - 2007/8
Y1 - 2007/8
N2 - 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.
AB - 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.
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U2 - 10.1093/nar/gkm569
DO - 10.1093/nar/gkm569
M3 - Article
C2 - 17686786
AN - SCOPUS:34548764367
SN - 0305-1048
VL - 35
SP - 5303
EP - 5311
JO - Nucleic acids research
JF - Nucleic acids research
IS - 16
ER -