Interactome of Two Diverse RNA Granules Links mRNA Localization to Translational Repression in Neurons
Interactome of Two Diverse RNA Granules Links mRNA Localization to Translational Repression in Neurons
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DOI：
10.1016/j.celrep.2013.11.023
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发表时间：
2013-12-01
期刊：
影响因子：
8.8
通讯作者：
Kiebler, Michael A.
中科院分区：
文献类型：
--
作者：
Fritzsche, Renate;Karra, Daniela;Kiebler, Michael A.
RNA 向树突的运输发生在神经元 RNA 颗粒中，这使得活性突触处按需合成特定蛋白质，从而有助于学习和记忆。为了深入了解控制树突 mRNA 定位和翻译的机制，我们建立了严格的方案来从大鼠脑中生化纯化 RNA 颗粒。在这里，我们鉴定了两种 RNA 结合蛋白（Barentsz 和 Staufen2）的一组特定相互作用子，这两种蛋白是神经元 RNA 颗粒的已知成分。首先，神经元 RNA 颗粒比之前预期的异质性要高得多，仅共享已识别蛋白质的三分之一。其次，树突状定位的 mRNA，例如。例如，Arc 和 CaMKII α，选择性地与不同的 RNA 颗粒结合。第三，我们的工作确定了一系列在 RNA 定位、翻译控制和 RNA 质量控制中具有已知作用的因素，这些因素可能使本地转录本处于翻译抑制状态，通常在不同类型的 RNP 中。
Transport of RNAs to dendrites occurs in neuronal RNA granules, which allows local synthesis of specific proteins at active synapses on demand, thereby contributing to learning and memory. To gain insight into the machinery controlling dendritic mRNA localization and translation, we established a stringent protocol to biochemically purify RNA granules from rat brain. Here, we identified a specific set of interactors for two RNA-binding proteins that are known components of neuronal RNA granules, Barentsz and Staufen2. First, neuronal RNA granules are much more heterogeneous than previously anticipated, sharing only a third of the identified proteins. Second, dendritically localized mRNAs, e. g., Arc and CaMKII alpha, associate selectively with distinct RNA granules. Third, our work identifies a series of factors with known roles in RNA localization, translational control, and RNA quality control that are likely to keep localized transcripts in a translationally repressed state, often in distinct types of RNPs.