Sanchez Mayka, Galy Bruno, Muckenthaler Martina U, Hentze Matthias W
Molecular Medicine Partnership Unit, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany.
Nat Struct Mol Biol. 2007 May;14(5):420-6. doi: 10.1038/nsmb1222. Epub 2007 Apr 8.
Hypoxia stimulates erythropoiesis, the major iron-utilization pathway. We report the discovery of a conserved, functional iron-responsive element (IRE) in the 5' untranslated region of the messenger RNA encoding endothelial PAS domain protein-1, EPAS1 (also called hypoxia-inducible factor-2alpha, HIF2alpha). Via this IRE, iron regulatory protein binding controls EPAS1 mRNA translation in response to cellular iron availability. Our results uncover a regulatory link that permits feedback control between iron availability and the expression of a key transcription factor promoting iron utilization. They also show that an IRE that is structurally distinct from, for example, the ferritin mRNA IRE and that has been missed by in silico approaches, can mediate mechanistically similar responses.
缺氧刺激红细胞生成，这是主要的铁利用途径。我们报告了在内皮PAS结构域蛋白1（EPAS1，也称为缺氧诱导因子-2α，HIF2α）编码信使核糖核酸的5'非翻译区发现了一个保守的功能性铁反应元件（IRE）。通过这个IRE，铁调节蛋白结合可根据细胞内铁的可用性控制EPAS1信使核糖核酸的翻译。我们的结果揭示了一种调节联系，允许在铁的可用性与促进铁利用的关键转录因子的表达之间进行反馈控制。它们还表明，一个在结构上与例如铁蛋白信使核糖核酸IRE不同且被计算机方法遗漏的IRE，可以介导机制上类似的反应。
