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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
5' Untranslated Regions / genetics
-
5' Untranslated Regions / physiology*
-
Acute Disease
-
Animals
-
Base Sequence
-
Codon, Initiator*
-
Gene Expression Regulation
-
Hindlimb / blood supply*
-
Humans
-
Ischemia / genetics*
-
Ischemia / metabolism
-
L Cells
-
Male
-
Mice
-
Mice, Transgenic
-
Molecular Sequence Data
-
Muscle, Skeletal / blood supply*
-
NIH 3T3 Cells
-
Neovascularization, Physiologic / genetics
-
Neovascularization, Physiologic / physiology
-
Organ Specificity
-
Protein Biosynthesis*
-
RNA, Messenger / biosynthesis
-
Reverse Transcriptase Polymerase Chain Reaction
-
Sequence Alignment
-
Sequence Homology, Nucleic Acid
-
Species Specificity
-
Stress, Physiological / genetics
-
Stress, Physiological / metabolism
-
Vascular Endothelial Growth Factor A / biosynthesis*
-
Vascular Endothelial Growth Factor A / genetics*
Substances
-
5' Untranslated Regions
-
Codon, Initiator
-
RNA, Messenger
-
VEGFA protein, human
-
Vascular Endothelial Growth Factor A
-
vascular endothelial growth factor A, mouse