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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 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.
Cited literature [53 references]
https://hal.archives-ouvertes.fr/hal-01543718
Contributor : Stephanie Bornes <>
Submitted on : Wednesday, June 21, 2017 - 11:19:48 AM
Last modification on : Wednesday, March 18, 2020 - 1:34:09 AM
Document(s) archivé(s) le : Saturday, December 16, 2017 - 2:30:23 AM
Contributor : Stephanie Bornes <>
Submitted on : Wednesday, June 21, 2017 - 11:19:48 AM
Last modification on : Wednesday, March 18, 2020 - 1:34:09 AM
Document(s) archivé(s) le : Saturday, December 16, 2017 - 2:30:23 AM
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