Translational induction of VEGF internal ribosome entry site elements during the early response to ischemic stress. - Archive ouverte HAL Access content directly
Journal Articles Circulation Research Year : 2007

Translational induction of VEGF internal ribosome entry site elements during the early response to ischemic stress.

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Abstract

Vascular endothelial growth factor-A (VEGF), a powerful factor involved in vasculogenesis and angiogenesis, is translationally regulated through 2 independent internal ribosome entry sites (IRESs A and B). IRESs enable an mRNA to be translated under conditions in which 5'-cap-dependent translation is inhibited, such as low oxygen stress. In the VEGF mRNA, IRES A influences translation at the canonical AUG codon, whereas the 5' IRES B element regulates initiation at an upstream, in frame CUG. In this study, we have developed transgenic mice expressing reporter genes under the control of these 2 IRESs. We reveal that although these IRESs display low activity in embryos and adult tissues, they permit efficient translation at early time points in ischemic muscle, a stress under which cap-dependent translation is inhibited. These results demonstrate the in vivo efficacy of the VEGF IRESs in response to a local environmental stress such as hypoxia.

Dates and versions

inserm-00409540 , version 1 (10-08-2009)

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Stéphanie Bornes, Leonel Prado-Lourenco, Amandine Bastide, Catherine Zanibellato, Jason S. Iacovoni, et al.. Translational induction of VEGF internal ribosome entry site elements during the early response to ischemic stress.. Circulation Research, 2007, 100 (3), pp.305-8. ⟨10.1161/01.RES.0000258873.08041.c9⟩. ⟨inserm-00409540⟩
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