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.

Sophie Bonnal (1) , Céline Schaeffer (2) , Laurent Créancier (3) , Simone Clamens (1) , Hervé Moine (2) , Anne-Catherine Prats (1) , Stéphan Vagner (1)

1 Hormones, facteurs de croissance et physiopathologie vasculaire
2 SMBMR - Structure des macromolécules biologiques et mécanismes de reconnaissance
3 Centre de Recherches Pierre Fabre

The 484-nucleotide (nt) alternatively translated region (ATR) of the human fibroblast growth factor 2 (FGF-2) mRNA contains four CUG and one AUG translation initiation codons. Although the 5'-end proximal CUG codon is initiated by a cap-dependent translation process, the other four initiation codons are initiated by a mechanism of internal entry of ribosomes. We undertook here a detailed analysis of the cis-acting elements defining the FGF-2 internal ribosome entry site (IRES). A thorough deletion analysis study within the 5'-ATR led us to define a 176-nt region as being necessary and sufficient for IRES function at four codons present in a downstream 308-nt RNA segment. Unexpectedly, a single IRES module is therefore responsible for translation initiation at four distantly localized codons. The determination of the FGF-2 5'-ATR RNA secondary structure by enzymatic and chemical probing experiments showed that the FGF-2 IRES contained two stem-loop regions and a G quartet motif that constitute novel structural determinants of IRES function.

Domaines: Médecine humaine et pathologie

Sophie Bonnal, Céline Schaeffer, Laurent Créancier, Simone Clamens, Hervé Moine, et al.. 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.: Structural determinants of the FGF-2 IRES. Journal of Biological Chemistry, 2003, 278 (41), pp.39330-6. ⟨10.1074/jbc.M305580200⟩. ⟨hal-00307489⟩