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.
Nucleic Acids Res. 2013 Sep;41(17):7997-8010. doi: 10.1093/nar/gkt539. Epub 2013 Jul 12.
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.
血管内皮生长因子 A（VEGF-A）是一种重要的分泌性有丝分裂原，对生理和病理血管生成至关重要。VEGF-A 的转录后调控发生在多个水平。首先，选择性剪接产生不同的转录变体，编码不同的异构体，它们在受体结合和细胞外定位方面表现出不同的生物学特性。其次，通过结合位于 3'非翻译区的富含 AU 的元件的稳定和不稳定蛋白，VEGF-A mRNA 的稳定性受到缺氧或生长因子等效应物的调节。第三，VEGF-A mRNA 的翻译是一个受控制的过程，涉及到选择性起始密码子、内部核糖体进入位点（IRES）、上游开放阅读框（uORF）、miRNA 靶向和 3'非翻译区的核酶。这些不同水平的调节协同作用，对 VEGF-A 变体的表达进行精细调控。这篇综述将集中讨论我们目前对调节细胞内 VEGF-A 水平的复杂转录后调控开关的认识，这是转录后调控的典范模型。
