Fibroblast Growth Factor 2 Internal Ribosome Entry Site (Ires) Activity Ex Vivo and in Transgenic Mice Reveals a Stringent Tissue-Specific Regulation
Open Access
- 10 July 2000
- journal article
- research article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 150 (1) , 275-281
- https://doi.org/10.1083/jcb.150.1.275
Abstract
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 (Ell) 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.Keywords
This publication has 36 references indexed in Scilit:
- Retroviral Vectors for the Expression of Two Genes in Human Multipotent Neural Precursors and Their Differentiated Neuronal and Glial ProgenyHuman Gene Therapy, 1999
- Translation of CUG- but not AUG-initiated forms of human fibroblast growth factor 2 is activated in transformed and stressed cells.The Journal of cell biology, 1996
- Abnormal bone growth and selective translational regulation in basic fibroblast growth factor (FGF-2) transgenic mice.Molecular Biology of the Cell, 1995
- Differential modulation of cell phenotype by different molecular weight forms of basic fibroblast growth factor: possible intracellular signaling by the high molecular weight forms.The Journal of cell biology, 1995
- Fibrolast growth factors in the nervous systemJournal of Neurobiology, 1994
- Potential oncogenic effects of basic fibroblast growth factor requires cooperation between CUG and AUG-initiated forms.Cell Regulation, 1991
- Selective expression of high molecular weight basic fibroblast growth factor confers a unique phenotype to NIH 3T3 cells.Cell Regulation, 1991
- Neovascularization is associated with a switch to the export of bFGF in the multistep development of fibrosarcomaCell, 1991
- Human basic fibroblast growth factor gene encodes four polypeptides: three initiate translation from non-AUG codons.Proceedings of the National Academy of Sciences, 1989
- High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons.Proceedings of the National Academy of Sciences, 1989