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An upstream open reading frame within an IRES controls expression of a specific VEGF-A isoform

Abstract : Vascular endothelial growth factor A (VEGF-A) is a potent secreted mitogen critical for physiological and pathological angiogenesis. Regulation of VEGF- A occurs at multiple levels, including transcription, mRNA stabilization, splicing, translation and differ- ential cellular localization of various isoforms. Recent advances in our understanding of the post- transcriptional regulation of VEGF-A are comprised of the identification of stabilizing mRNA-binding proteins and the discovery of two internal ribosomal entry sites (IRES) as well as two alternative initiation codons in the 5 ’ UTR of the VEGF-A mRNA. We have previously reported that VEGF-A translation initia- tion at both the AUG and CUG codons is dependent on the exon content of the coding region. In this report, we show that the expression of different VEGF-A isoforms is regulated by a small upstream open reading frame (uORF) located within an inter- nal ribosome entry site, which is translated through a cap-independent mechanism. This uORF acts as a cis -regulatory element that regulates negatively the expression of the VEGF 121 isoform. Our data provide a framework for understanding how VEGF- A mRNAs are translated, and how the production of the VEGF 121 isoform is secured under non-hypoxic environmental conditions.
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Amandine Bastide, Zeineb Karaa, Sté Phanie Bornes, Corinne Hieblot, Eric Lacazette, et al.. An upstream open reading frame within an IRES controls expression of a specific VEGF-A isoform. Nucleic Acids Research, Oxford University Press, 2008, 36, pp.2434 - 2445. ⟨10.1093/nar/gkn093⟩. ⟨hal-01543718⟩

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