scholarly journals A Single Internal Ribosome Entry Site Containing a G Quartet RNA Structure Drives Fibroblast Growth Factor 2 Gene Expression at Four Alternative Translation Initiation Codons

2003 ◽  
Vol 278 (41) ◽  
pp. 39330-39336 ◽  
Author(s):  
Sophie Bonnal ◽  
Céline Schaeffer ◽  
Laurent Créancier ◽  
Simone Clamens ◽  
Hervé Moine ◽  
...  
1995 ◽  
Vol 15 (1) ◽  
pp. 35-44 ◽  
Author(s):  
S Vagner ◽  
M C Gensac ◽  
A Maret ◽  
F Bayard ◽  
F Amalric ◽  
...  

Alternative initiations of translation of the human fibroblast growth factor 2 (FGF-2) mRNA, at three CUG start codons and one AUG start codon, result in the synthesis of four isoforms of FGF-2. This process has important consequences on the fate of FGF-2: the CUG-initiated products are nuclear and their constitutive expression is able to induce cell immortalization, whereas the AUG-initiated product, mostly cytoplasmic, can generate cell transformation. Thus, the different isoforms probably have distinct targets in the cell. We show here that translation initiation of the FGF-2 mRNA breaks the rule of the cap-dependent ribosome scanning mechanism. First, translation of the FGF-2 mRNA was shown to be cap independent in vitro. This cap-independent translation required a sequence located between nucleotides (nt) 192 and 256 from the 5' end of the 318-nt-long 5' untranslated region. Second, expression of bicistronic vectors in COS-7 cells indicated that the FGF-2 mRNA is translated through a process of internal ribosome entry mediated by the mRNA leader sequence. By introducing additional AUG codons into the RNA leader sequence, we localized an internal ribosome entry site to between nt 154 and 318 of the 5' untranslated region, just upstream of the first CUG. The presence of an internal ribosome entry site in the FGF-2 mRNA suggests that the process of internal translation initiation, by controlling the expression of a growth factor, could have a crucial role in the control of cell proliferation and differentiation.


2000 ◽  
Vol 150 (1) ◽  
pp. 275-281 ◽  
Author(s):  
Laurent Créancier ◽  
Dominique Morello ◽  
Pascale Mercier ◽  
Anne-Catherine Prats

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.


2004 ◽  
Vol 18 (13) ◽  
pp. 1583-1585 ◽  
Author(s):  
Shigetada Teshima‐Kondo ◽  
Kazumi Kondo ◽  
Leonel Prado‐Lourenco ◽  
Irma Gabriela Gonzalez‐Herrera ◽  
Kazuhito Rokutan ◽  
...  

FEBS Letters ◽  
1998 ◽  
Vol 434 (3) ◽  
pp. 417-420 ◽  
Author(s):  
Diane L Miller ◽  
Justin A Dibbens ◽  
Annette Damert ◽  
Werner Risau ◽  
Mathew A Vadas ◽  
...  

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