Translational induction of VEGF internal ribosome entry site elements during the early response to ischemic stress.
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.
Bornes
Stéphanie
S
INSERM U858, Université Paul Sabatier, IFR31, BP 84225, 31432 Toulouse Cedex 04, France.
Prado-Lourenco
Leonel
L
Bastide
Amandine
A
Zanibellato
Catherine
C
Iacovoni
Jason S
JS
Lacazette
Eric
E
Prats
Anne-Catherine
AC
Touriol
Christian
C
Prats
Hervé
H
D020121:5' Untranslated Regions / Q000235:genetics / Q000502:physiology*; D000208:Acute Disease; D000818:Animals; D001483:Base Sequence; D018387:Codon, Initiator; D005786:Gene Expression Regulation; D006614:Hindlimb / Q000098:blood supply*; D006801:Humans; D007511:Ischemia / Q000235:genetics* / Q000378:metabolism; D007739:L Cells; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000098:blood supply*; D041681:NIH 3T3 Cells; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology; D009928:Organ Specificity; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics*
D020121:5' Untranslated Regions; D018387:Codon, Initiator; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse