Rouault T A, Haile D J, Downey W E, Philpott C C, Tang C, Samaniego F, Chin J, Paul I, Orloff D, Harford J B
Cell Biology and Metabolism Branch, National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD 20892.
Biometals. 1992 Autumn;5(3):131-40. doi: 10.1007/BF01061319.
Post-transcriptional regulation of genes important in iron metabolism, ferritin and the transferrin receptor (TfR), is achieved through regulated binding of a cytosolic protein, the iron-responsive element binding protein (IRE-BP), to RNA stem-loop motifs known as iron-responsive elements (IREs). Binding of the IRE-BP represses ferritin translation and represses degradation of the TfR mRNA. The IRE-BP senses iron levels and accordingly modifies binding to IREs through a novel sensing mechanism. An iron-sulfur cluster of the IRE-BP reversibly binds iron; when cytosolic iron levels are depleted, the cluster becomes depleted of iron and the IRE-BP acquires the capacity to bind IREs. When cytosolic iron levels are replete, the IRE-BP loses RNA binding capacity, but acquires enzymatic activity as a functional aconitase. RNA binding and aconitase activity are mutually exclusive activities of the IRE-BP, and the state of the iron-sulfur cluster determines how the IRE-BP will function.
铁代谢过程中重要基因（铁蛋白和转铁蛋白受体（TfR））的转录后调控，是通过一种胞质蛋白——铁反应元件结合蛋白（IRE-BP）与称为铁反应元件（IREs）的RNA茎环基序的特异性结合来实现的。IRE-BP的结合会抑制铁蛋白的翻译，并抑制TfR mRNA的降解。IRE-BP能够感知铁水平，并通过一种全新的感应机制相应地改变与IREs的结合。IRE-BP的一个铁硫簇可逆地结合铁；当胞质铁水平降低时，该簇中铁含量减少，IRE-BP获得与IREs结合的能力。当胞质铁水平充足时，IRE-BP失去RNA结合能力，但获得了作为功能性乌头酸酶的酶活性。RNA结合和乌头酸酶活性是IRE-BP相互排斥的活动，铁硫簇的状态决定了IRE-BP的功能方式。
