Huntingtin protein, mutated in Huntington’s disease, is implicated in nucleic acid–mediated processes, yet the evidence for direct huntingtin–nucleic acid interaction is limited. Here, we show wild-type and mutant huntingtin copurify with nucleic acids, primarily RNA, and interact directly with G-rich RNAs in in vitro assays. Huntingtin RNA-immunoprecipitation sequencing from patient-derived fibroblasts and neuronal progenitor cells expressing wild-type and mutant huntingtin revealed long noncoding RNA NEAT1 as a significantly enriched transcript. Altered NEAT1 levels were evident in Huntington’s disease cells and postmortem brain tissues, and huntingtin knockdown decreased NEAT1 levels. Huntingtin colocalized with NEAT1 in paraspeckles, and we identified a high-affinity RNA motif preferred by huntingtin. This study highlights NEAT1 as a huntingtin interactor, demonstrating huntingtin’s involvement in RNA-mediated functions and paraspeckle regulation.

中文翻译：

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亨廷顿蛋白是一种 RNA 结合蛋白，参与 NEAT1 介导的副斑点


亨廷顿蛋白在亨廷顿病中发生突变，与核酸介导的过程有关，但亨廷顿蛋白与核酸直接相互作用的证据有限。在这里，我们展示了野生型和突变型亨廷顿蛋白与核酸（主要是 RNA）共纯化，并在体外测定中直接与富含 G 的 RNA 相互作用。对表达野生型和突变型亨廷顿蛋白的患者来源的成纤维细胞和神经元祖细胞进行亨廷顿蛋白 RNA 免疫沉淀测序，揭示了长非编码 RNA整洁1作为显着丰富的转录本。改变整洁1亨廷顿舞蹈症细胞和死后脑组织中的水平很明显，亨廷顿蛋白敲低减少整洁1水平。亨廷顿蛋白共定位于整洁1在副斑雀中，我们鉴定了亨廷顿偏好的高亲和力 RNA 基序。本研究亮点整洁1作为亨廷顿蛋白相互作用子，证明亨廷顿蛋白参与 RNA 介导的功能和副斑调节。