VEGF-A mRNA processing, stability and translation: a paradigm for intricate regulation of gene expression at the post-transcriptional level.
VEGF-A mRNA processing, stability and translation: a paradigm for intricate regulation of gene expression at the post-transcriptional level.
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DOI：
10.1093/nar/gkt539
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发表时间：
2013-09
影响因子：
14.9
通讯作者：
Touriol C
中科院分区：
文献类型：
--
作者：
Arcondéguy T;Lacazette E;Millevoi S;Prats H;Touriol C
血管内皮生长因子A（VEGF-A）是一种分泌型促有丝分裂原，对生理和病理性血管生成至关重要。VEGF-A的转录后调节发生在多个水平。首先，选择性剪接产生编码不同同种型的不同转录物变体，所述同种型在受体结合和细胞外定位方面表现出不同的生物学特性。第二，VEGF-A mRNA的稳定性受缺氧或生长因子等效应物的调节，通过稳定和不稳定蛋白与位于3′-非翻译区的富含AU的元件结合。第三，VEGF-A mRNA的翻译是一个受控的过程，包括可变起始密码子、内部核糖体进入位点（IRES）、上游开放阅读框（uORF）、miRNA靶向以及3′端非翻译区的核糖开关。这些不同水平的调控共同作用，对VEGF-A变体的表达进行了关键性的微调。这篇评论将集中在我们目前的知识，复杂的转录后调节开关，调节细胞VEGF-A水平，转录后调节的典范模型。
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.
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