IRP-1 binding to ferritin mRNA prevents the recruitment of the small ribosomal subunit by the cap-binding complex elF4F
IRP-1 binding to ferritin mRNA prevents the recruitment of the small ribosomal subunit by the cap-binding complex elF4F
复制标题
DOI：
10.1016/s1097-2765(00)80282-8
复制
发表时间：
1998-09-01
期刊：
影响因子：
16
通讯作者：
Hentze, MW
中科院分区：
文献类型：
--
作者：
Muckenthaler, M;Gray, NK;Hentze, MW
铁调节蛋白 (IRP) 与位于铁蛋白 H 链和 L 链 mRNA 帽结构附近的 IRE 结合，通过阻止小核糖体亚基募集到 mRNA 来阻断铁蛋白合成。我们设计了一种新的程序来检查翻译起始因子 (eIF) 在受调节 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（包括 eIF4E、eIF4G 和 eIF4A）也会组装。这种组装是徒劳的，因为在 IRP-1 存在的情况下，无法建立 eIF4F 和小核糖体亚基之间的桥接相互作用。我们的研究结果提供了对 mRNA 结合蛋白在翻译起始因子水平上的翻译控制的深入了解，并揭示了铁稳态的关键调节步骤。
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.