A CYTOSOLIC PROTEIN BINDS TO STRUCTURAL ELEMENTS WITHIN THE IRON REGULATORY REGION OF THE TRANSFERRIN RECEPTOR MESSENGER-RNA
A CYTOSOLIC PROTEIN BINDS TO STRUCTURAL ELEMENTS WITHIN THE IRON REGULATORY REGION OF THE TRANSFERRIN RECEPTOR MESSENGER-RNA
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DOI：
10.1073/pnas.86.10.3574
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发表时间：
1989-05-01
影响因子：
11.1
通讯作者：
HARFORD, JB
中科院分区：
文献类型：
--
作者：
KOELLER, DM;CASEY, JL;HARFORD, JB
转铁蛋白受体(TFR)的编码水平受铁的调节，这种调节是由TFR转录本的3‘’非翻译区(UTR-)的一部分介导的。人转铁蛋白基因3‘’非编码区的这一部分包含5个RNA元件，它们在结构上与铁反应元件(IRE)具有相似的结构，在铁蛋白的5‘’非编码区中发现单个拷贝，铁蛋白的翻译是由铁调节的。此外，在鸡TFR基因的3‘’非编码区中也含有5个非常相似的元件。利用RNaseT1保护的凝胶漂移分析表明，人类细胞系的胞浆提取物中含有一种能够与人TfR3‘’UTR特异相互作用的IRE结合蛋白。当保护蛋白被去除时，受保护的RNA可以被RNaseT1消化，产生具有TfR3‘’UTR中包含的两个IRES特征的寡核苷酸片段。通过交叉竞争实验判断，相同的IRE结合蛋白取决于RNA的序列。基于实验证明至少存在两个IRE样结构元件，提出了TFR mRNA调节区的全面二级结构。
The level of mRNA encoding the transferrin receptor (TfR) is regulated by iron, and this regulation is mediated by a portion of the 3'' untranslated region (UTR-) of the TfR transcript. This portion of 3'' UTR of the human TfR mRNA contains five RNA elements that have structural similarity to the iron-responsive element (IRE) found as a single copy in the 5'' UTR of the mRNA for ferritin, whose translation is regulation by iron. Moreover, five very similar elements are also contained in the 3'' UTR of the chicken TfR mRNA. Cytosolic extracts of human cell lines are shown by a gel shift assay involving RNase T1 protection to contain an IRE-binding protein capable of specific interaction with the human TfR 3'' UTR. When the protecting protein is removed, the protected RNA can be digested with RNase T1 to yield oligoribonucleotide fragments characteristics of two of the IREs contained in the TfR3'' UTR. As judged by cross-competition experiments, the same IRE-binding protein is shown to depend upon the sequence of the RNA. A comprehensive secondary structure for the regulatory region of the TfR mRNA is proposed based on the experimentally demonstrated presence of at least two IRE-like structural elements.