RGD Reference Report - The nonsense-mediated decay pathway and mutually exclusive expression of alternatively spliced FGFR2IIIb and -IIIc mRNAs. - Rat Genome Database

RGD Reference Report - The nonsense-mediated decay pathway and mutually exclusive expression of alternatively spliced FGFR2IIIb and -IIIc mRNAs. - Rat Genome Database

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General

The nonsense-mediated decay pathway and mutually exclusive expression of alternatively spliced FGFR2IIIb and -IIIc mRNAs.
Authors:	Jones, RB Wang, F Luo, Y Yu, C Jin, C Suzuki, T Kan, M McKeehan, WL
Citation:	Jones RB, etal., J Biol Chem. 2001 Feb 9;276(6):4158-67. Epub 2000 Oct 20.
RGD ID:	2289853
Pubmed:	PMID:11042206 (View Abstract at PubMed)
DOI:	DOI:10.1074/jbc.M006151200 (Journal Full-text)
Exons IIIb and IIIc of the FGFR2 gene are alternatively spliced in a mutually exclusive manner in different cell types. A switch from expression of FGFR2IIIb to FGFR2IIIc accompanies the transition of nonmalignant rat prostate tumor epithelial cells (DTE) to cells comprising malignant AT3 tumors. Here we used transfection of minigenes with and without alterations in reading frame and with and without introns to examine how translation affects observed FGFR2 splice products. We observed that nonsense mutations in other than the last exon led to a dramatic reduction in mRNA that is abrogated by removal of downstream introns in both DTE and AT3 cells. The mRNA, devoid of both IIIb and IIIc exons (C1-C2), is a major splice product from minigenes lacking an intron downstream of the second common exon C2. From these observations, we suggest that repression of exon IIIc and activation of exon IIIb inclusion in DTE cells lead to the generation of both C1-IIIb-C2 and C1-C2 products. However, the C1-C2 product from the native gene is degraded due to a frameshift and a premature termination codon caused by splicing C1 and C2 together. Derepression of exon IIIc and repression of exon IIIb lead to the generation of both C1-IIIc-C2 and C1-C2 products in AT3 cells, but the C1-C2 product is degraded. The C1-IIIb-IIIc-C2 mRNA containing a premature termination codon in exon IIIc was present, but at apparently trace levels in both cell types. The nonsense-mediated mRNA decay pathway and cell type-dependent rates of inclusion of exons IIIb and IIIc result in the mutually exclusive expression of FGFR2IIIb and IIIc.

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Molecular Function

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
fibroblast growth factor binding		IPI	FGF7 (Homo sapiens)	2289853	Fgfr2IIIb/Kgfr isoform	RGD
fibroblast growth factor binding		IPI	UniProtKB:P03968	2289853		RGD

Objects Annotated

Genes (Rattus norvegicus)

Fgfr2 (fibroblast growth factor receptor 2)

Additional Information