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Multiple interdependent sequence elements control splicing of a fibroblast growth factor receptor 2 alternative exon
F Del Gatto1, A Plet, M C Gesnel
1INSERM U463, Institut de Biologie-CHR, Nantes, France.
Molecular and Cellular Biology
|September 1, 1997
Summary
This study identifies new sequences that control K-SAM exon splicing in epithelial cells. These intron sequences, IAS2 and IAS3, work together to regulate fibroblast growth factor receptor 2 gene expression.
Area of Science:
- Molecular Biology
- Gene Regulation
- RNA Splicing
Background:
- Fibroblast growth factor receptor 2 (FGFR2) gene alternative splicing.
- K-SAM exon splicing is specific to epithelial cells.
- Previous identification of cis-acting elements controlling K-SAM exon splicing.
Purpose of the Study:
- Identify novel regulatory elements involved in K-SAM exon splicing.
- Elucidate the mechanism of K-SAM exon splicing regulation.
Main Methods:
- Site-directed mutagenesis.
- RNA secondary structure analysis.
- Exon splicing assays.
Main Results:
- Two novel intron-activating sequences (IAS2 and IAS3) downstream of the K-SAM exon were identified.
- IAS3 contains a region that can form an RNA secondary structure with IAS2.
- Mutations disrupting this structure decrease splicing activation, while compensatory mutations restore it.
Conclusions:
- Multiple, interdependent sequence elements in the pre-mRNA regulate K-SAM exon splicing.
- A model for K-SAM exon splicing involving RNA secondary structure formation is proposed.
- These findings contribute to understanding alternative splicing in gene regulation.