An intronic sequence element mediates both activation and repression of rat fibroblast growth factor receptor 2 pre-mRNA splicing

Russ P. Carstens, Wallace L. Mckeehan, Mariano Garcia-Blanco

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Alternative splicing of fibroblast growth factor receptor 2 (FGF-R2) is an example of highly regulated alternative splicing in which exons IIIb and IIIc are utilized in a mutually exclusive manner in different cell types. The importance of this splicing choice is highlighted by studies which indicate that deregulation of the FGF-R2 splicing is associated with progression of prostate cancer. Loss of expression of a IIIb exon-containing isoform of FGF- R2 [FGF-R2 (IIIb)] accompanies the transition of a well-differentiated, androgen-dependent rat prostate cancer cell line, DT3, to the more aggressive, androgen-independent AT3 cell line. We have used transfection of rat FGF-R2 minigenes into DT3 and AT3 cancer cell lines to study the mechanisms that control alternative splicing of rat FGF-R2. Our results support a model in which an important cis-acting element located in the intron between these alternative exons mediates activation of splicing using the upstream IIIb exon and repression of the downstream IIIc exon in DT3 cells. This element consists of 57 nucleotides (nt) beginning 917 nt downstream of the IIIb exon. Analysis of mutants further demonstrates that an 18-nt 'core sequence' within this element is most crucial for its function. Based on our observations, we have termed this sequence element ISAR (for intronic splicing activator and repressor), and we suggest that factors which bind this sequence are required for maintenance of expression of the FGF-R2 (IIIb) isoform.

Original languageEnglish (US)
Pages (from-to)2205-2217
Number of pages13
JournalMolecular and Cellular Biology
Volume18
Issue number4
StatePublished - Apr 1998
Externally publishedYes

Fingerprint

RNA Precursors
Receptor, Fibroblast Growth Factor, Type 2
Exons
Alternative Splicing
Cell Line
Androgens
Prostatic Neoplasms
Protein Isoforms
Nucleotides
Introns
Transfection
rat Fgfr2 protein
Maintenance
Neoplasms

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

An intronic sequence element mediates both activation and repression of rat fibroblast growth factor receptor 2 pre-mRNA splicing. / Carstens, Russ P.; Mckeehan, Wallace L.; Garcia-Blanco, Mariano.

In: Molecular and Cellular Biology, Vol. 18, No. 4, 04.1998, p. 2205-2217.

Research output: Contribution to journalArticle

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