Functional signature for the recognition of specific target mRNAs by human Staufen1 protein.
Functional signature for the recognition of specific target mRNAs by human Staufen1 protein.
复制标题
通过人Staufen1蛋白识别特定靶标mRNA的功能签名。
DOI：
10.1093/nar/gku073
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发表时间：
2014-04
影响因子：
14.9
通讯作者：
Ortín J
中科院分区：
文献类型：
--
作者：
de Lucas S;Oliveros JC;Chagoyen M;Ortín J
细胞信使RNA（mRNA）以核糖核蛋白颗粒的形式与蛋白质结合。双链RNA结合蛋白（DRB）在mRNA的合成、修饰、活性和降解中起着重要作用。Staufen是一种DRB蛋白，参与果蝇早期发育过程中特定mRNA的定位翻译。人Staufen 1（hStau 1）可形成RNA颗粒，该颗粒含有翻译调节蛋白以及细胞骨架和马达蛋白，以允许颗粒在微管上运动，但hStau 1-RNA识别的机制尚不清楚。在这里，我们使用了亲和层析，RNA酶保护，深度测序和生物信息学分析的组合，以确定mRNA差异相关的hStau 1或突变蛋白不能结合RNA，并以这种方式，定义了一个集合的mRNA特异性相关野生型hStau 1。由两个相反极性Alu基序组成的共同序列特征存在于hStau 1相关mRNA中，并且被证明足以结合hStau 1和hStau 1依赖性刺激蛋白质表达。我们的研究结果揭示了hStau 1如何识别广泛的细胞靶mRNA，以控制其定位，表达和命运。
Cellular messenger RNAs (mRNAs) are associated to proteins in the form of ribonucleoprotein particles. The double-stranded RNA-binding (DRB) proteins play important roles in mRNA synthesis, modification, activity and decay. Staufen is a DRB protein involved in the localized translation of specific mRNAs during Drosophila early development. The human Staufen1 (hStau1) forms RNA granules that contain translation regulation proteins as well as cytoskeleton and motor proteins to allow the movement of the granule on microtubules, but the mechanisms of hStau1-RNA recognition are still unclear. Here we used a combination of affinity chromatography, RNAse-protection, deep-sequencing and bioinformatic analyses to identify mRNAs differentially associated to hStau1 or a mutant protein unable to bind RNA and, in this way, defined a collection of mRNAs specifically associated to wt hStau1. A common sequence signature consisting of two opposite-polarity Alu motifs was present in the hStau1-associated mRNAs and was shown to be sufficient for binding to hStau1 and hStau1-dependent stimulation of protein expression. Our results unravel how hStau1 identifies a wide spectrum of cellular target mRNAs to control their localization, expression and fate.
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影响因子：
11.4
作者：
Ferrandon, D;Koch, I;NussleinVolhard, C
通讯作者：
NussleinVolhard, C
影响因子：
14.9
作者：
Falcón, AM;Fortes, P;Ortín, J
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Ortín, J
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de Lucas, Susana;Peredo, Joan;Ortin, Juan
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Ortin, Juan
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Boccaccio, Graciela L.
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16.2
作者：
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Hirokawa, N