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Journal articles
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 differential cellular localization of various isoforms. Recent advances in our understanding of the posttranscriptional 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 initiation 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 internal 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.
Cited literature [53 references]
https://www.hal.inserm.fr/inserm-00408822
Contributor : Marie Francoise Simon <>
Submitted on : Thursday, August 20, 2009 - 2:18:33 PM
Last modification on : Friday, January 10, 2020 - 9:09:08 PM
Long-term archiving on: : Tuesday, June 15, 2010 - 10:00:17 PM
Contributor : Marie Francoise Simon <>
Submitted on : Thursday, August 20, 2009 - 2:18:33 PM
Last modification on : Friday, January 10, 2020 - 9:09:08 PM
Long-term archiving on: : Tuesday, June 15, 2010 - 10:00:17 PM
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