Kikinis Z, Eisenstein R S, Bettany A J, Munro H N
Division of Toxicology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Nucleic Acids Res. 1995 Oct 25;23(20):4190-5. doi: 10.1093/nar/23.20.4190.
Iron regulates synthesis of the iron storage protein ferritin at the translational level through interaction between a stem-loop structure, the iron-responsive element (IRE), located in the 5'-untranslated region (5'-UTR) of ferritin mRNAs, and a protein, the iron regulatory protein (IRP). The role of IRE secondary structure in translational regulation of ferritin synthesis was explored by introducing ferritin constructs containing mutations in the IRE into Rat-2 fibroblasts. Our in vivo studies demonstrate that size and sequence of the loop within the IRE and the distance and/or spatial relationship of this loop to the bulged nucleotide region closest to the loop must be preserved in order to observe iron-dependent translation of ferritin mRNA. In contrast, changes in nucleotide sequence of the upper stem can be introduced without affecting translational regulation in vivo, as long as a stem can be formed. Our in vivo results suggest that only a very small variation in the affinity of interaction of IRP with IRE can be tolerated in order to maintain iron-dependent regulation of translation.
铁通过位于铁蛋白mRNA 5'非翻译区（5'-UTR）的茎环结构——铁反应元件（IRE），与一种蛋白质——铁调节蛋白（IRP）之间的相互作用，在翻译水平上调节铁储存蛋白铁蛋白的合成。通过将含有IRE突变的铁蛋白构建体导入大鼠2成纤维细胞，研究了IRE二级结构在铁蛋白合成翻译调控中的作用。我们的体内研究表明，为了观察铁蛋白mRNA的铁依赖性翻译，IRE内环的大小和序列以及该环与最靠近环的凸起核苷酸区域的距离和/或空间关系必须保持不变。相比之下，只要能形成茎，上茎核苷酸序列的改变就可以引入而不影响体内的翻译调控。我们的体内结果表明，为了维持铁依赖性的翻译调控，IRP与IRE相互作用的亲和力只能容忍非常小的变化。
