Regulation of ferritin and transferrin receptor mRNAs.
Regulation of ferritin and transferrin receptor mRNAs.
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DOI：
10.1016/s0021-9258(19)34036-0
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发表时间：
1990-03
期刊：
影响因子：
--
通讯作者：
Elizabeth C. Theil
中科院分区：
文献类型：
--
作者：
Elizabeth C. Theil
铁通过新的mRNA/蛋白质相互作用调节铁代谢关键的两种蛋白质铁蛋白和转铁蛋白受体的合成。mRNA调节序列（铁响应元件（IRE））出现在所有铁蛋白mRNA的5 '非翻译区，并在转铁蛋白受体mRNA的3'非翻译区以五种变异形式重复。当铁过量时，铁蛋白合成和铁储存增加。同时，转铁蛋白受体的合成和铁的摄取减少。在两种mRNA的不同非编码区中的共同IRE调控序列的位置可以解释铁如何具有相反的代谢效应;当IRE位于铁蛋白mRNA的5 '-非翻译区时，过量的铁增强翻译，而转铁蛋白受体mRNA的3'-非翻译区中IRE的存在导致铁依赖性降解。铁究竟是如何起作用的以及在何处起作用还不清楚.最近从肝脏和红细胞中纯化到均一的可溶性90-kDa调节蛋白特异性阻断铁蛋白mRNA的翻译并结合IRE序列，但似乎不是铁结合蛋白。该蛋白是第一个被鉴定的特异性真核mRNA调节因子，并证实了20年前的预测。铁蛋白和转铁蛋白受体mRNA的铁的协调调节也可以定义一个更一般的策略，使用共同的mRNA序列来协调代谢相关蛋白质的合成。
Iron regulates the synthesis of two proteins critical for iron metabolism, ferritin and the transferrin receptor, through novel mRNA/protein interactions. The mRNA regulatory sequence (iron-responsive element (IRE)) occurs in the 5'-untranslated region of all ferritin mRNAs and is repeated as five variations in the 3'-untranslated region of transferrin receptor mRNA. When iron is in excess, ferritin synthesis and iron storage increase. At the same time, transferrin receptor synthesis and iron uptake decrease. Location of the common IRE regulatory sequence in different noncoding regions of the two mRNAs may explain how iron can have opposite metabolic effects; when the IRE is in the 5'-untranslated region of ferritin mRNA, translation is enhanced by excess iron whereas the presence of the IREs in the 3'-untranslated region of the transferrin receptor mRNA leads to iron-dependent degradation. How and where iron actually acts is not yet known. A soluble 90-kDa regulatory protein which has been recently purified to homogeneity from liver and red cells specifically blocks translation of ferritin mRNA and binds IRE sequences but does not appear to be an iron-binding protein. The protein is the first specific eukaryotic mRNA regulator identified and confirms predictions 20 years old. Concerted regulation by iron of ferritin and transferrin receptor mRNAs may also define a more general strategy for using common mRNA sequences to coordinate the synthesis of metabolically related proteins.