Translational Control in Neurons

神经元的翻译控制

• 批准号: 7097943
• 负责人: HENRI TIEDGE
• 金额: $ 28.39万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7097943
• 关键词: SDS polyacrylamide gel electrophoresis; Xenopus oocyte; gel mobility shift assay; gene expression; genetic translation; immunoprecipitation; laboratory rat; neural plasticity; neurons; polyadenylate; small nuclear RNA; synapses; synaptosomes

REVISED ABSTRACT: DESCRIPTION (provided by applicant): Long-term plastic changes at the synapse require de novo synthesis of proteins. Part of this requirement, it is suggested, is met by translation in situ of mRNAs that are localized to postsynaptic microdomains. Local translation, according to this model, provides the spatial and temporal specificity that is necessary for input-dependent modulations of synaptic protein repertoires. A central requisite for this concept is the control of gene expression at the level of translation. In particular, to afford spatio-temporal specificity, translational machinery in neurons will have to be tightly controlled such that protein synthesis is enabled only at the right place and at the right time. What are the functional mechanisms of such translational control, and how are they regulated? In the research project proposed here, it is hypothesized that small RNAs play an instrumental role in translational control mechanisms in neurons. Specifically, it is conjectured that non-translatable dendritic BC1 RNA operates as a repressor in the translation initiation pathway. To test this hypothesis, we will dissect structure-function relationships that are underlying BC1-mediated translational repression mechanisms. The analysis will be directed at the functional relevance of the BC1 domain architecture, and at the functional targets of BC1 RNA in the translation initiation pathway. BC1-mediated repression will also be functionally ascertained in living cells, using model systems such as Xenopus oocytes. It is the overall goal of the proposed research to elucidate mechanisms and functional significance of local translational control mediated by small neuronal RNAs.

修订摘要：描述（申请人提供）： 突触时的长期塑性变化需要从头合成蛋白质。建议通过将其本地定位于突触后微区域的mRNA的原位翻译来满足这一要求的一部分。根据该模型，局部翻译提供了对突触蛋白库的输入依赖性调制所必需的空间和时间特异性。该概念的主要必要条件是控制基因表达在翻译水平上。特别是，为了获得时空特异性，必须严格控制神经元中的翻译机械，以使蛋白质合成仅在正确的位置和正确的时间才能启用。这种翻译控制的功能机制是什么？如何调节？在此处提出的研究项目中，假设小型RNA在神经元的翻译控制机制中起了工具作用。具体而言，猜想是不可转移的树突BC1 RNA在翻译起始途径中充当阻遏物。为了检验这一假设，我们将剖析基础BC1介导的翻译抑制机制的结构功能关系。该分析将针对BC1域结构的功能相关性，以及在翻译起始途径中BC1 RNA的功能目标。 BC1介导的抑制也将在活细胞中使用模型系统（例如爪蟾卵母细胞）在功能上确定。这是拟议研究的总体目标，即阐明由小型神经元RNA介导的局部翻译控制的机制和功能意义。