A Role for Huntington Disease Protein in Dendritic RNA Granules*
A Role for Huntington Disease Protein in Dendritic RNA Granules*
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DOI：
10.1074/jbc.m110.114561
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发表时间：
2010-02
期刊：
影响因子：
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通讯作者：
J. Savas;Bin Ma;K. Deinhardt;B. P. Culver;S. Restituito;Ligang Wu;J. Belasco;M. Chao;N. Tanese
中科院分区：
文献类型：
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作者：
J. Savas;Bin Ma;K. Deinhardt;B. P. Culver;S. Restituito;Ligang Wu;J. Belasco;M. Chao;N. Tanese
神经元中mRNA的调节运输和局部翻译对于调节突触强度、维持适当的神经回路和建立长期记忆至关重要。神经元RNA颗粒是核糖核蛋白颗粒，其用于沿沿着微管运输mRNA并响应突触活动控制局部蛋白质合成。研究表明，神经元RNA颗粒与体细胞P体具有相似的结构和功能。我们最近报道了亨廷顿病蛋白亨廷顿蛋白（Htt）与Argonaute（Ago）相关并定位于细胞质P体，其作为mRNA储存、降解和小RNA介导的基因沉默的位点。在这里，我们报告说，野生型Htt协会与Ago 2和神经元颗粒的成分和共同交通与树突中的mRNA。发现Htt与含有已知树状靶向mRNA的3′-非翻译区序列的RNA共定位。在神经元中敲低Htt引起mRNA的定位改变。当拴在一个报告构建体，Htt下调报告基因表达的方式依赖于Ago 2，这表明，Htt的功能可能会抑制mRNA在神经元颗粒运输过程中的翻译。
Regulated transport and local translation of mRNA in neurons are critical for modulating synaptic strength, maintaining proper neural circuitry, and establishing long term memory. Neuronal RNA granules are ribonucleoprotein particles that serve to transport mRNA along microtubules and control local protein synthesis in response to synaptic activity. Studies suggest that neuronal RNA granules share similar structures and functions with somatic P-bodies. We recently reported that the Huntington disease protein huntingtin (Htt) associates with Argonaute (Ago) and localizes to cytoplasmic P-bodies, which serve as sites of mRNA storage, degradation, and small RNA-mediated gene silencing. Here we report that wild-type Htt associates with Ago2 and components of neuronal granules and co-traffics with mRNA in dendrites. Htt was found to co-localize with RNA containing the 3′-untranslated region sequence of known dendritically targeted mRNAs. Knockdown of Htt in neurons caused altered localization of mRNA. When tethered to a reporter construct, Htt down-regulated reporter gene expression in a manner dependent on Ago2, suggesting that Htt may function to repress translation of mRNAs during transport in neuronal granules.