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首页> 外文期刊>PLoS Genetics >Genome-Wide Analysis of Histidine Repeats Reveals Their Role in the Localization of Human Proteins to the Nuclear Speckles Compartment
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Genome-Wide Analysis of Histidine Repeats Reveals Their Role in the Localization of Human Proteins to the Nuclear Speckles Compartment

机译：组氨酸重复序列的全基因组分析揭示了它们在人类蛋白质定位于核斑点室中的作用

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Single amino acid repeats are prevalent in eukaryote organisms, although the role of many such sequences is still poorly understood. We have performed a comprehensive analysis of the proteins containing homopolymeric histidine tracts in the human genome and identified 86 human proteins that contain stretches of five or more histidines. Most of them are endowed with DNA- and RNA-related functions, and, in addition, there is an overrepresentation of proteins expressed in the brain and/or nervous system development. An analysis of their subcellular localization shows that 15 of the 22 nuclear proteins identified accumulate in the nuclear subcompartment known as nuclear speckles. This localization is lost when the histidine repeat is deleted, and significantly, closely related paralogous proteins without histidine repeats also fail to localize to nuclear speckles. Hence, the histidine tract appears to be directly involved in targeting proteins to this compartment. The removal of DNA-binding domains or treatment with RNA polymerase II inhibitors induces the re-localization of several polyhistidine-containing proteins from the nucleoplasm to nuclear speckles. These findings highlight the dynamic relationship between sites of transcription and nuclear speckles. Therefore, we define the histidine repeats as a novel targeting signal for nuclear speckles, and we suggest that these repeats are a way of generating evolutionary diversification in gene duplicates. These data contribute to our better understanding of the physiological role of single amino acid repeats in proteins.
机译：单个氨基酸重复在真核生物中很普遍，尽管许多这样的序列的作用仍知之甚少。我们对人类基因组中含有均聚组氨酸片段的蛋白质进行了全面分析，并鉴定出包含五个或更多组氨酸片段的86种人类蛋白质。它们中的大多数具有与DNA和RNA相关的功能，此外，在大脑和/或神经系统发育中表达的蛋白质过多。对它们的亚细胞定位的分析表明，鉴定出的22种核蛋白中有15种聚集在称为核斑点的核子室中。当删除组氨酸重复时，该定位丢失，并且明显地，没有组氨酸重复的紧密相关的旁系同源蛋白质也不能定位于核斑点。因此，组氨酸束似乎直接参与将蛋白质靶向该区室。去除DNA结合结构域或用RNA聚合酶II抑制剂处理可诱导几个含有多组氨酸的蛋白质从核质到核斑点的重新定位。这些发现突出了转录位点与核斑点之间的动态关系。因此，我们将组氨酸重复定义为核斑点的新型靶向信号，并且我们建议这些重复是一种在基因重复中产生进化多样化的方式。这些数据有助于我们更好地了解蛋白质中单个氨基酸重复序列的生理作用。

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