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Originally published In Press as doi:10.1074/jbc.M908431199 on April 14, 2000

J. Biol. Chem., Vol. 275, Issue 25, 19361-19367, June 23, 2000
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Alternative Translation Initiation of Human Fibroblast Growth Factor 2 mRNA Controlled by Its 3'-Untranslated Region Involves a Poly(A) Switch and a Translational Enhancer*

Christian TouriolDagger , Myriam Roussigne§, Marie-Claire Gensac, Hervé Prats, and Anne-Catherine Prats

From INSERM U397, Endocrinologie et Communication Cellulaire, Institut Louis Bugnard, C.H.U. Rangueil, Avenue Jean Poulhès, 31403 Toulouse Cedex 04, France

Five fibroblast growth factor 2 (FGF-2) isoforms are synthesized from human FGF-2 mRNA by a process of alternative initiation of translation. The regulation of FGF-2 isoform expression by the mRNA 5823-nucleotide-long 3'-untranslated region containing eight alternative polyadenylation sites was examined. Because previous studies had shown that FGF-2 expression was regulated in primary cells but not in transformed cells, primary human skin fibroblasts were used in this study. Using an approach of cell transfection with synthetic reporter mRNAs, a novel translational enhancer (3'-TE) was identified in the 1370-nucleotide mRNA segment located upstream from the eighth poly(A) site. Deletion mutagenesis showed that the 3'-TE was composed of two domains with additive effects. The 3'-TE exhibited the unique feature of modulating the use of FGF-2 alternative initiation codons, which favored the relative expression of CUG-initiated isoforms. Interestingly, the use of an alternative polydenylation site removing the 3'-TE was detected in skin fibroblasts in response to heat shock and cell density variations. At high cell densities, 3'-TE removal was correlated with a loss of CUG-initiated FGF-2 expression. These data show that the FGF-2 mRNA 3'-untranslated region is able to modulate FGF-2 isoform expression by the coupled processes of translation activation and alternative polyadenylation.


* This work was supported by grants from the Association pour la Recherche sur le Cancer, the Ligue Nationale contre le Cancer, and the Conseil Régional Midi-Pyrénées and by European Community Biotechnology program (subprogram Cell Factory, Actions de Recherches Concertées) Grant 94/99-181.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Recipient of successive fellowships from the Ministère de l'Education Nationale et de la Recherche and from the Ligue Nationale contre le Cancer. Present address: Unité de Physiologie Cellulaire et Moléculaire, CNRS ERS 1590, 31059 Toulouse Cedex, France.

§ Present address: Institut de Pharmacologie et de Biochimie Structurale, CNRS UPR 9062, 105, route de Narbonne, 31062 Toulouse Cedex, France.

To whom correspondence should be addressed. Tel.: 33-561-32-21-42; Fax: 33-561-32-21-41; E-mail: pratsac@rangueil.inserm.fr.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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