Small RNAs in Neurons

描述（由申请人提供）：调节RNA是真核细胞中基因表达的重要介质。BC RNA是一种神经元调节RNA亚型，是翻译抑制因子，参与突触局部蛋白质合成的控制。基因表达的原位翻译调控被认为是突触连接长期结构和功能可塑性的主要机制之一。神经元中的局部翻译控制途径的关键条件是选择性递送各种RNA组分，特别是调节RNA，至神经元树突分支内的不同突触后靶位点。RNA是如何指定这种靶向递送的？生理刺激和/或人造药物又是如何调节这种靶向递送的？ 在这里提出的研究项目中，假设神经元BC RNA使用建筑基序来传达空间信息。有人建议，这样的图案指定在突触树突状神经元域的差异的目的地网站。本研究的主要目的是通过破译神经元BC RNA中的空间信息编码来验证这一假设。在该项目的第一部分中，计划对BC RNA中的差异树枝状靶向能力进行功能解剖。RNA基序将被确定，直接组成和条件树突状靶向，分别。该项目的第二部分将重点关注神经元中RNA空间编码的调制。计划确定树突状RNA靶向机制是否受到受体刺激的调节，以及人造药物是否影响和调节这些机制。 总之，计划的研究是针对神经元调控RNA中空间信息编码的生理意义。 公共卫生相关性：神经元npcRNA中的空间信息编码，据推测，是一个关键的先决条件，本地的翻译控制机制，是潜在的长期突触可塑性。计划中的研究针对靶向npcRNA递送到突触树突目的地位点的机制和调节。对神经元中空间RNA编码的分子理解将使我们能够理解其在神经元可塑性、药物作用和人类疾病中的相关性。

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.