Small RNAs in Neurons

神经元中的小 RNA

• 批准号: 8808747
• 负责人: HENRI TIEDGE
• 金额: $ 39.65万
• 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 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8808747
• 关键词: Address; Adenosine; Alzheimer' s Disease; Binding; Biochemical; Cellular biology; Code; Data; Defect; Dendrites; Destinations; Disease; Dissection; Divalent Cations; Elements; FXTAS; Goals; Guanosine; Health; Lead; Link; Mediating; Messenger RNA; Molecular; Nature; Neuronal Plasticity; Neurons; Nucleotides; Property; Protein Biosynthesis; Proteins; RNA; RNA Transport; Receptor Activation; Research; Role; Site; Small RNA; Specific qualifier value; Specificity; Stimulus; Synapses; System; Testing; To specify; Translations; Trust; Variant; Work; base; experience; hnRNP A2; insight; instrument; mutant; receptor; targeted delivery

DESCRIPTION (provided by applicant): In neurons, local protein synthesis is an important instrument in the modulation of synaptic strength. The specificity of this mechanism is determined, at least in part, by the identity of mRNAs that are locally available for on-site translation. The targeted delivery of select RNAs to synapto-dendritic domains is therefore a key underpinning of neuronal function and plasticity. For this reason, it is essential that we understand molecular information coding mechanisms that specify and implement dendritic targeting of neuronal RNAs. Our understanding of dendritic RNA targeting mechanisms has remained rudimentary, despite progress in recent years. At a most fundamental level, we need to identify and comprehend the codes that are used by RNAs to specify synapto-dendritic delivery. We need to decipher conditional codes, i.e. those contained in RNA targeting elements that specify inducible targeting. We need to gain insight into mechanisms that targeting factors use to decode such elements and initiate targeting in an activity-dependent manner. To address these critical issues in neuronal cell biology, the proposed project will conduct a functional dissection of the molecular and cellular basis of dendritic RNA targeting mechanisms. The planned research will be directed at the overarching hypothesis that noncanonical RNA motifs serve as dendritic targeting code determinants. Specifically, Aim 1 will address the question whether noncanonical targeting motif subtypes carry discrete spatial codes that are determinants of conditional vs. constitutive dendritic RNA transport. Aim 2 will test the hypothesis that motif codes are recognized by cognate dendritic targeting factors, and that differential recognition specifies conditional vs. constitutive transport. Aim 3 will establish whether conditional dendritic RNA targeting mediated by such motifs is inducible by neuronal activity and receptor activation. It will be the long-term goal of the planned project to arrive ata molecular understanding of neuronal mechanisms that mediate activity-dependent RNA transport in dendrites.

描述（由申请人提供）：在神经元中，局部蛋白质合成是突触强度调节的重要工具。这种机制的特异性至少部分通过当地可用于现场翻译的mRNA的身份确定。因此，将精选的RNA靶向递送到突触神经域是神经元功能和可塑性的关键基础。因此，我们必须了解指定和实施神经元RNA的树突状靶向的分子信息编码机制。 尽管近年来进展，我们对树突状RNA靶向机制的理解仍然是基本的。在最基本的层面上，我们需要识别和理解RNA使用的代码来指定synapto dendritic交付。我们需要破译条件代码，即RNA靶向元素中指定诱导靶向的代码。我们需要深入了解靶向因素用于解码此类元素并以活动依赖性方式启动靶向的机制。为了解决神经元细胞生物学中的这些关键问题，提出的项目将对树突状RNA靶向机制的分子和细胞基础进行功能解剖。 计划的研究将针对总体假设，即非规范RNA图案是树突状靶向代码决定因素。具体而言，AIM 1将解决以下问题，非规范靶向基序子类型是否携带离散的空间代码，这些空间代码是条件性和组成型树突状RNA转运的决定因素。 AIM 2将检验以下假设：基序代码是由同源树突靶因子识别的，并且差异识别指定条件性与本构运输。 AIM 3将确定该基序介导的条件树突状RNA是否通过神经元活性和受体激活诱导。计划项目的长期目标是使ATA对介导树突中依赖活性RNA转运的神经元机制的分子理解。