SEQUENCING OF THE HUMAN VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) 3'-UNTRANSLATED REGION (UTR) - CONSERVATION OF 5 HYPOXIA-INDUCIBLE RNA-PROTEIN BINDING-SITES

Vascular endothelial growth factor (VEGF) is a potent angiogenic facto r whose mRNA expression is induced by hypoxia. This induction is due i n large part to an increase in the stability of its mRNA. The RNA sequ ences and cognate proteins responsible for this increased stability wi th hypoxia are not well understood. In order to identify regions of fu nctional importance in the 3'UTR of VEGF mRNA, we have sequenced the h uman VEGF 3'UTR and compared it to the rat sequence. Overall sequence homology was 82% with complete conservation of all four potential poly adenylation signals and both nonameric instability elements. Five hypo xia-inducible RNA protein-binding (HI-RPB) sites were identified by si tes bind a similar or related protein complex. On average, the five si tes were 95% conserved at the nucleotide level between the rat and cor responding human sequence. This conservation taken together with sever al previously described, independent correlations between the presence of these RNA-protein complexes and an increase in VEGF mRNA stability suggest an important functional role for these sites in mediating hyp oxia-inducible VEGF mRNA stability.