Muckenthaler M, Gray N K, Hentze M W
Gene Expression Programme, European Molecular Biology Laboratory, Heidelberg Germany.
Mol Cell. 1998 Sep;2(3):383-8. doi: 10.1016/s1097-2765(00)80282-8.
Binding of iron regulatory proteins (IRPs) to IREs located in proximity to the cap structure of ferritin H- and L-chain mRNAs blocks ferritin synthesis by preventing the recruitment of the small ribosomal subunit to the mRNA. We have devised a novel procedure to examine the assembly of translation initiation factors (eIFs) on regulated mRNAs. Unexpectedly, we find that the cap binding complex eIF4F (comprising eIF4E, eIF4G, and eIF4A) assembles even when IRP-1 is bound to the cap-proximal IRE. This assembly is futile, because bridging interactions between eIF4F and the small ribosomal subunit cannot be established in the presence of IRP-1. Our findings provide insight into translational control by an mRNA binding protein at the level of translation initiation factors and uncover a key regulatory step in iron homeostasis.
铁调节蛋白（IRPs）与位于铁蛋白H链和L链mRNA帽结构附近的铁反应元件（IREs）结合，通过阻止小核糖体亚基与mRNA结合来阻断铁蛋白的合成。我们设计了一种新方法来检测翻译起始因子（eIFs）在受调控mRNA上的组装。出乎意料的是，我们发现即使IRP-1与帽近端IRE结合，帽结合复合物eIF4F（由eIF4E、eIF4G和eIF4A组成）仍会组装。这种组装是无效的，因为在IRP-1存在的情况下，eIF4F与小核糖体亚基之间无法建立桥接相互作用。我们的研究结果为mRNA结合蛋白在翻译起始因子水平上的翻译控制提供了见解，并揭示了铁稳态中的一个关键调节步骤。
