Eukaryotic initiation factor 4a3 is a selenium-regulated RNA-binding protein that selectively inhibits selenocysteine incorporation.
Eukaryotic initiation factor 4a3 is a selenium-regulated RNA-binding protein that selectively inhibits selenocysteine incorporation.
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DOI：
10.1016/j.molcel.2009.06.026
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发表时间：
2009-08-28
期刊：
影响因子：
16
通讯作者：
Driscoll DM
中科院分区：
文献类型：
--
作者：
Budiman ME;Bubenik JL;Miniard AC;Middleton LM;Gerber CA;Cash A;Driscoll DM
硒蛋白的合成需要将UGA终止密码子翻译重新编码为硒代半胱氨酸。在缺硒期间，存在硒蛋白表达的等级，某些硒蛋白以牺牲其他硒蛋白为代价合成。限制硒代半胱氨酸掺入机制优先用于维持必需硒蛋白的表达的机制尚未阐明。在这里，我们证明，真核起始因子4a3（eIF4a3）参与硒蛋白的一个子集的翻译控制。eIF4a3与硒蛋白mRNA的相互作用阻止了硒代半胱氨酸插入所需的SECIS结合蛋白2的结合，从而抑制了硒蛋白的合成。此外，eIF4a3的表达响应于硒而被调节。基于敲低和过表达研究，eIF4a3是必要的，足以介导细胞中的选择性翻译抑制。我们的研究结果支持eIF4a3链接硒状态与差异硒蛋白表达的模型。
The synthesis of selenoproteins requires the translational recoding of the UGA stop codon as selenocysteine. During selenium deficiency, there is a hierarchy of selenoprotein expression, with certain selenoproteins synthesized at the expense of others. The mechanism by which the limiting selenocysteine incorporation machinery is preferentially utilized to maintain the expression of essential selenoproteins has not been elucidated. Here, we demonstrate that eukaryotic initiation factor 4a3 (eIF4a3) is involved in the translational control of a subset of selenoproteins. The interaction of eIF4a3 with the selenoprotein mRNA prevents the binding of SECIS binding Protein 2, which is required for selenocysteine insertion, thereby inhibiting the synthesis of the selenoprotein. Furthermore, the expression of eIF4a3 is regulated in response to selenium. Based on knockdown and overexpression studies, eIF4a3 is necessary and sufficient to mediate selective translational repression in cells. Our results support a model in which eIF4a3 links selenium status with differential selenoprotein expression.
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影响因子：
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DOI：
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发表时间：
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影响因子：
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