Fibroblast growth factor 2 (FGF-2) is a powerful mitogen involved in proliferation, differentiation, and survival of various cells including neurons. FGF-2 expression is translationally regulated; in particular, the FGF-2 mRNA contains an internal ribosome entry site (IRES) allowing cap-independent translation. Here, we have analyzed FGF-2 IRES tissue specificity ex vivo and in vivo by using a dual luciferase bicistronic vector. This IRES was active in most transiently transfected human and nonhuman cell types, with a higher activity in p53 −/− osteosarcoma and neuroblastoma cell lines. Transgenic mice were generated using bicistronic transgenes with FGF-2 IRES or encephalomyocarditis virus (EMCV) IRES. Measurements of luciferase activity revealed high FGF-2 IRES activity in 11-d-old embryos (E11) but not in the placenta; activity was high in the heart and brain of E16. FGF-2 IRES activity was low in most organs of the adult, but exceptionally high in the brain. Such spatiotemporal variations were not observed with the EMCV IRES. These data, demonstrating the strong tissue specificity of a mammalian IRES in vivo, suggest a pivotal role of translational IRES- dependent activation of FGF-2 expression during embryogenesis and in adult brain. FGF-2 IRES could constitute, thus, a powerful tool for gene transfer in the central nervous system.
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10 July 2000
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July 10 2000
Fibroblast Growth Factor 2 Internal Ribosome Entry Site (Ires) Activity Ex Vivo and in Transgenic Mice Reveals a Stringent Tissue-Specific Regulation
Laurent Créancier,
Laurent Créancier
aInstitut National de la Santé et de la Recherche Médicale U397, Endocrinologie et Communication Cellulaire, Institut Fédératif de Recherche Louis Bugnard, C.H.U. Rangueil, 31403 Toulouse Cedex 04, France
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Dominique Morello,
Dominique Morello
bCentre de Biologie du Développement, UMR 5547, Université Paul Sabatier, Bâtiment 4R3, 118 Route de Narbonne, 31062 Toulouse Cedex 04, France
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Pascale Mercier,
Pascale Mercier
cInstitut de Pharmacologie et Biologie Structurale, UPR 9062, 31077 Toulouse Cedex 04, France
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Anne-Catherine Prats
Anne-Catherine Prats
aInstitut National de la Santé et de la Recherche Médicale U397, Endocrinologie et Communication Cellulaire, Institut Fédératif de Recherche Louis Bugnard, C.H.U. Rangueil, 31403 Toulouse Cedex 04, France
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Laurent Créancier
aInstitut National de la Santé et de la Recherche Médicale U397, Endocrinologie et Communication Cellulaire, Institut Fédératif de Recherche Louis Bugnard, C.H.U. Rangueil, 31403 Toulouse Cedex 04, France
Dominique Morello
bCentre de Biologie du Développement, UMR 5547, Université Paul Sabatier, Bâtiment 4R3, 118 Route de Narbonne, 31062 Toulouse Cedex 04, France
Pascale Mercier
cInstitut de Pharmacologie et Biologie Structurale, UPR 9062, 31077 Toulouse Cedex 04, France
Anne-Catherine Prats
aInstitut National de la Santé et de la Recherche Médicale U397, Endocrinologie et Communication Cellulaire, Institut Fédératif de Recherche Louis Bugnard, C.H.U. Rangueil, 31403 Toulouse Cedex 04, France
Abbreviations used in this paper: CMV, cytomegalovirus; CNS, central nervous system; EMV, encephalomyocarditis virus; IRES, internal ribosome entry site; RT, reverse transcriptase.
Received:
April 17 2000
Revision Requested:
May 26 2000
Accepted:
May 30 2000
Online ISSN: 1540-8140
Print ISSN: 0021-9525
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Cell Biol (2000) 150 (1): 275–281.
Article history
Received:
April 17 2000
Revision Requested:
May 26 2000
Accepted:
May 30 2000
Citation
Laurent Créancier, Dominique Morello, Pascale Mercier, Anne-Catherine Prats; Fibroblast Growth Factor 2 Internal Ribosome Entry Site (Ires) Activity Ex Vivo and in Transgenic Mice Reveals a Stringent Tissue-Specific Regulation. J Cell Biol 10 July 2000; 150 (1): 275–281. doi: https://doi.org/10.1083/jcb.150.1.275
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