Nucleolin binds to a subset of selenoprotein mRNAs and regulates their expression.
Nucleolin binds to a subset of selenoprotein mRNAs and regulates their expression.
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DOI：
10.1093/nar/gkq247
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发表时间：
2010-08
影响因子：
14.9
通讯作者：
Driscoll DM
中科院分区：
文献类型：
--
作者：
Miniard AC;Middleton LM;Budiman ME;Gerber CA;Driscoll DM
硒是人体必需的微量元素，以第21位氨基酸硒代半胱氨酸（Sec）的形式存在于硒蛋白中。为了合成硒蛋白，必须发生翻译重编程事件，因为Sec由UGA终止密码子编码。在哺乳动物中，将UGA重新编码为Sec依赖于硒代半胱氨酸插入序列（SECIS）元件，即转录物3′非翻译区的茎环结构。SECIS作为RNA结合蛋白的平台，介导或调节重编码机制。使用UV交联，我们确定了一个110 kDa的蛋白质，它结合了高亲和力的SECIS元素从硒蛋白mRNA的一个子集。通过RNA亲和层析纯化交联活性，并通过质谱分析鉴定为核仁素。在体外结合试验表明，纯化的核仁素歧视SECIS元素在其他因素的情况下。基于siRNA实验，核仁素是某些硒蛋白的最佳表达所必需的。核仁素对SECIS的亲和力与其对硒蛋白表达的影响之间存在良好的相关性。由于硒蛋白的转录水平和定位在siRNA处理的细胞中没有改变，我们的研究结果表明核仁素选择性地增强了硒蛋白在翻译水平上的一个子集的表达。
Selenium, an essential trace element, is incorporated into selenoproteins as selenocysteine (Sec), the 21st amino acid. In order to synthesize selenoproteins, a translational reprogramming event must occur since Sec is encoded by the UGA stop codon. In mammals, the recoding of UGA as Sec depends on the selenocysteine insertion sequence (SECIS) element, a stem-loop structure in the 3′ untranslated region of the transcript. The SECIS acts as a platform for RNA-binding proteins, which mediate or regulate the recoding mechanism. Using UV crosslinking, we identified a 110 kDa protein, which binds with high affinity to SECIS elements from a subset of selenoprotein mRNAs. The crosslinking activity was purified by RNA affinity chromatography and identified as nucleolin by mass spectrometry analysis. In vitro binding assays showed that purified nucleolin discriminates among SECIS elements in the absence of other factors. Based on siRNA experiments, nucleolin is required for the optimal expression of certain selenoproteins. There was a good correlation between the affinity of nucleolin for a SECIS and its effect on selenoprotein expression. As selenoprotein transcript levels and localization did not change in siRNA-treated cells, our results suggest that nucleolin selectively enhances the expression of a subset of selenoproteins at the translational level.
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影响因子：
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作者：
Barel, Monique;Hovanessian, Ara G.;Meibom, Karin;Briand, Jean-Paul;Dupuis, Marion;Charbit, Alain
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Gladyshev, Vadim N.
影响因子：
3.9
作者：
Bermano, G;Nicol, F;Hesketh, JE
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