title: VEGF-A mRNA processing, stability and translation: a paradigm for intricate regulation of gene expression at the post-transcriptional level.
abstract: Vascular Endothelial Growth Factor A (VEGF-A) is a potent secreted mitogen crucial for physiological and pathological angiogenesis. Post-transcriptional regulation of VEGF-A occurs at multiple levels. Firstly, alternative splicing gives rise to different transcript variants encoding diverse isoforms that exhibit distinct biological properties with regard to receptor binding and extra-cellular localization. Secondly, VEGF-A mRNA stability is regulated by effectors such as hypoxia or growth factors through the binding of stabilizing and destabilizing proteins at AU-rich elements located in the 3'-untranslated region. Thirdly, translation of VEGF-A mRNA is a controlled process involving alternative initiation codons, internal ribosome entry sites (IRESs), an upstream open reading frame (uORF), miRNA targeting and a riboswitch in the 3' untranslated region. These different levels of regulation cooperate for the crucial fine-tuning of the expression of VEGF-A variants. This review will be focused on our current knowledge of the complex post-transcriptional regulatory switches that modulate the cellular VEGF-A level, a paradigmatic model of post-transcriptional regulation.
authors.affiliation: Inserm UMR1037, Centre de Recherches en Cancérologie de Toulouse, CHU Rangueil, BP84225, 31432 Toulouse Cedex 4, France and Université Toulouse III Paul-Sabatier, 118 Route de Narbonne, 31400 Toulouse, France.
authors.forename: Tania
authors.initials: T
authors.lastname: Arcondéguy
authors.forename: Eric
authors.initials: E
authors.lastname: Lacazette
authors.forename: Stefania
authors.initials: S
authors.lastname: Millevoi
authors.forename: Hervé
authors.initials: H
authors.lastname: Prats
authors.forename: Christian
authors.initials: C
authors.lastname: Touriol
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D014176:Protein Biosynthesis; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A