Small RNAs in Neurons

神经元中的小 RNA

• 批准号: 7851178
• 负责人: HENRI TIEDGE
• 金额: $ 39.64万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7851178
• 关键词: Amphetamines; BC1 RNA; Brain; Code; Competence; Decision Making; Dendrites; Destinations; Dissection; Distal; Drug Addiction; Drug effect disorder; Elements; Equilibrium; Eukaryotic Cell; Gene Expression; Goals; Maintenance; Medial; Mediating; Mediator of activation protein; Molecular; Nature; Neuronal Plasticity; Neurons; Pathway interactions; Pharmaceutical Preparations; Physiological; Play; Process; Protein Biosynthesis; Proteins; RNA; RNA Transport; RNA-Protein Interaction; Receptor Activation; Regulation; Repression; Research; Research Project Grants; Role; Site; Small RNA; Specific qualifier value; Specificity; Stimulus; Structure; Sympathomimetics; Synapses; Synaptic plasticity; Testing; Trans-Activators; Translations; Variant; analog; authority; base; experience; hnRNP A2; human disease; neuronal cell body; postsynaptic; premature; public health relevance; receptor; response; stem; targeted delivery

DESCRIPTION (provided by applicant): Regulatory RNAs are important mediators of gene expression in eukaryotic cells. BC RNAs, a neuronal subtype of regulatory RNAs, are translational repressors that have been implicated in the control of local protein synthesis at the synapse. On-site translational control of gene expression is now seen as one of the major mechanisms underlying the long-term structural and functional plasticity of synaptic connections. A key requisite for the local translational control pathway in neurons is the selective delivery of various RNA components, in particular of regulatory RNAs, to diverse postsynaptic target sites within neuronal dendritic arborizations. How is such targeted delivery specified by RNAs, and how is it modulated by physiological stimuli and/or man-made drugs? In the research project proposed here, it is hypothesized that neuronal BC RNAs use architectural motifs to convey spatial information. It is suggested that such motifs specify differential destination sites in synapto-dendritic neuronal domains. It is the main objective of the present proposal to test this hypothesis by deciphering spatial information coding in neuronal BC RNAs. In the first part of the project, it is planned to conduct a functional dissection of differential dendritic targeting competence in BC RNAs. RNA motifs will be identified that direct constitutive and conditional dendritic targeting, respectively. The second part of the project will focus on modulation of RNA spatial coding in neurons. It is planned to establish whether dendritic RNA targeting mechanisms are subject to regulation by receptor stimulation, and whether man-made drugs impact and modulate these mechanisms. In summary, the planned research is directed at the physiological significance of spatial information coding in neuronal regulatory RNAs. PUBLIC HEALTH RELEVANCE: Spatial information coding in neuronal npcRNAs, it is hypothesized, is a key prerequisite for local translational control mechanisms that are underlying long-term synaptic plasticity. The planned research is directed at mechanism and modulation of targeted npcRNA delivery to synapto-dendritic destination sites. A molecular understanding of spatial RNA coding in neurons will enable us to appreciate its relevance in neuronal plasticity, drug action, and human disease.

描述（由申请人提供）：调节性RNA是真核细胞中基因表达的重要介体。 BC RNA是调节性RNA的神经元亚型，是转化阻遏物，与控制突触时局部蛋白质合成有关。现在，基因表达的现场翻译控制被视为突触连接长期结构和功能可塑性的主要机制之一。神经元中局部翻译控制途径的关键必需是选择性递送各种RNA成分，尤其是调节性RNA，以在神经元树突状营养中的各种突触后靶位点进行选择。 RNA指定的靶向递送是如何通过生理刺激和/或人造药物调节的？ 在此处提出的研究项目中，假设神经元BC RNA使用建筑图案传达空间信息。建议这种基序在突触神经元结构域中指定差异目的地位点。通过在神经元BC RNA中解密空间信息编码来检验这一假设是本提案的主要目标。在该项目的第一部分中，计划在BC RNA中对差异树突靶向能力进行功能解剖。 RNA基序将分别鉴定出直接构成和条件树突靶向。该项目的第二部分将集中于神经元中RNA空间编码的调节。计划确定树突状RNA靶向机制是否受受体刺激调节，以及人造药物是否影响和调节这些机制。 总而言之，计划的研究针对神经元调节RNA中空间信息编码的生理意义。 公共卫生相关性：假设神经元NPCRNA中的空间信息编码是局部翻译控制机制的关键先决条件，这些机制是基本的长期突触可塑性。该计划的研究针对靶向NPCRNA递送到突触的树枝状目的地位置的机理和调节。对神经元中空间RNA编码的分子理解将使我们能够欣赏其在神经元可塑性，药物作用和人类疾病中的相关性。