IRON REGULATES FERRITIN MESSENGER-RNA TRANSLATION THROUGH A SEGMENT OF ITS 5' UNTRANSLATED REGION
IRON REGULATES FERRITIN MESSENGER-RNA TRANSLATION THROUGH A SEGMENT OF ITS 5' UNTRANSLATED REGION
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DOI：
10.1073/pnas.84.23.8478
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发表时间：
1987-12-01
影响因子：
11.1
通讯作者：
MUNRO, HN
中科院分区：
文献类型：
--
作者：
AZIZ, N;MUNRO, HN
在以前的研究中，我们表明，急性铁给药完整的大鼠或大鼠肝癌细胞培养诱导铁储存蛋白铁蛋白的合成激活翻译无活性的细胞质铁蛋白mRNA的重（H）和轻（L）亚基。在活化过程中，这些铁蛋白mRNA被募集到多核糖体上。为了阐明这些参与铁翻译反应的mRNA的结构特征，将铁蛋白L亚基mRNA的5“和3”非翻译区（UTR）与细菌氯霉素乙酰转移酶（CAT）mRNA的阅读框融合，构建了嵌合体。通过逆转录病毒介导的基因转移，将该嵌合体及其衍生的缺失构建体导入大鼠肝癌细胞系。完整的嵌合体显示出响应于培养基的铁富集而增加的CAT活性，而5“UTR的前67个核苷酸（其含有高度保守的序列）的缺失导致铁调节的丧失。然而，位于许多基因的5“侧翼区的顺式作用序列已经反复参与调节其转录表达，我们在这里报告了在真核mRNA的5”UTR内发现的特异性调节翻译序列。
In previous studies, we showed that acute administration of iron to intact rats or to rat hepatoma cells in culture induces synthesis of the iron-storage protein ferritin by activating translation of inactive cytoplasmic ferritin mRNAs for both the heavy (H) and the light (L) subunits. In the course of activation, these ferritin mRNAs are recruited onto polysomes. To elucidate the structural features of these mRNAs involved in the translational response to iron, a chimera was constructed from the 5'' and 3'' untranslated regions (UTRs) of ferritin L subunit mRNA fused to the reading frame of the mRNA of bacterial chloramphenicol acetyltransferase (CAT). This chimera and deletion constructs derived from it were introduced into a rat hepatoma cell line by retrovirus-mediated gene transfer. The complete chimera showed increased CAT activity in response to iron enrichment of the medium, whereas deletion of the first 67 nucleotides of the 5'' UTR, which contain a highly conserved sequence, caused loss of regulation by iron. Whereas cis-acting sequences located in the 5'' flanking regions of many genes have been repeatedly implicated in modulating their transcriptional expression, we report here a specific regulatory translational sequence found within the 5'' UTR of a eukaryotic mRNA.