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首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >RNA binding activity of the recessive parkinsonism protein DJ-1 supports involvement in multiple cellular pathways
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RNA binding activity of the recessive parkinsonism protein DJ-1 supports involvement in multiple cellular pathways

机译：隐性帕金森病蛋白DJ-1的RNA结合活性支持参与多种细胞途径

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摘要

Parkinson's disease (PD) is a major neurodegenerative condition with several rare Mendelian forms. Oxidative stress and mitochondrial function have been implicated in the pathogenesis of PD but the molecular mechanisms involved in the degeneration of neurons remain unclear. DJ-1 mutations are one cause of recessive parkinsonism, but this gene is also reported to be involved in cancer by promoting Ras signaling and suppressing PTEN-induced apoptosis. The specific function of DJ-1 is unknown, although it is responsive to oxidative stress and may play a role in the maintenance of mitochondria. Here, we show, using four independent methods, that DJ-1 associates with RNA targets in cells and the brain, including mitochondrial genes, genes involved in glutathione metabolism, and members of the PTEN/PI3K cascade. Pathogenic recessive mutants are deficient in this activity. We show that DJ-1 is sufficient for RNA binding at nanomolar concentrations. Further, we show that DJ-1 binds RNA but dissociates after oxidative stress. These data implicate a single mechanism for the pleiotropic effects of DJ-1 in different model systems, namely that the protein binds multiple RNA targets in an oxidation-dependent manner.
机译：帕金森氏病（PD）是一种主要的神经退行性疾病，有几种罕见的孟德尔形式。氧化应激和线粒体功能已牵涉PD的发病机理，但涉及神经元变性的分子机制仍不清楚。 DJ-1突变是造成隐性帕金森病的原因之一，但据报道该基因还通过促进Ras信号传导和抑制PTEN诱导的细胞凋亡而参与了癌症。 DJ-1的具体功能未知，尽管它对氧化应激有反应，并可能在线粒体的维持中发挥作用。在这里，我们使用四种独立的方法显示DJ-1与细胞和大脑中的RNA靶标相关，包括线粒体基因，涉及谷胱甘肽代谢的基因以及PTEN / PI3K级联成员。致病性隐性突变体缺乏这种活性。我们显示DJ-1足以在纳摩尔浓度的RNA结合。此外，我们显示DJ-1结合RNA，但在氧化应激后解离。这些数据暗示了在不同模型系统中DJ-1的多效性作用的单一机制，即该蛋白质以氧化依赖性方式结合了多个RNA靶标。

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