Shedding light on the role of RNA binding protein-mediated RNA regulation in synaptic plasticity
揭示 RNA 结合蛋白介导的 RNA 调节在突触可塑性中的作用
基本信息
- 批准号:10285142
- 负责人:
- 金额:$ 6.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-30 至 2022-12-29
- 项目状态:已结题
- 来源:
- 关键词:Affinity ChromatographyAllelesAlternative SplicingAxonBioinformaticsBiological AssayBiologyBrainBreedingCaliberCell NucleusCellsComplexDNADataData SetDendritesDiseaseEnvironmentFMR1Fluorescent in Situ HybridizationFoundationsGene ExpressionGenesGenetic TranscriptionHigh-Throughput Nucleotide SequencingHippocampus (Brain)Immediate-Early GenesImmunoprecipitationKnowledgeLaboratoriesLearningLightLightingMeasuresMediatingMemoryMessenger RNAMethodologyModelingMolecularMusNeurologicNeuronsNeuropilNeurosciencesOpticsPathologicPoly APopulationProcessProtein BiosynthesisProteomeRNARNA BindingRNA metabolismRNA-Binding ProteinsRegulationResearchResolutionRestRoleSiteStructureSynapsesSynaptic plasticityTechnologyTestingTimeTranscriptTranslationsUniversitiesUp-Regulationcalmodulin-dependent protein kinase IIcell typecrosslinkexcitatory neuronexperienceexperimental studygenetic informationin vivoinsightinterestmRNA Precursormouse modelnervous system disorderneuronal cell bodynovelnovel strategiesoptogeneticsprotein distributionrelating to nervous systemresponseunpublished works
项目摘要
Project Summary
Neurons have highly specialized structures and functions; their genetic information is often located a great
distance from the sites where information gets transmitted, and they must dynamically alter the synaptic
proteome in response to neural activity. These challenges indicate that neurons have evolved unique regulatory
mechanisms to meet functional demands. The uniformity of DNA across different cell types suggests that how
genetic information is unfolded and processed underlies cellular diversity. In this view, careful examination of the
regulation of RNA metabolism, how pre-mRNA gene copies are alternatively spliced and polyadenylated, edited,
localized, and translationally regulated, will offer a new avenue towards understanding complex processes, such
as synaptic plasticity underlying learning and memory. This notion has driven molecular neuroscientists to search
for factors that localize and regulate synaptic RNAs. We are only beginning to compile a list of these key
regulators, such as RNA binding proteins (RBPs), particularly in the synapses of hippocampal neurons that are
involved in memory, and to date very little is known about how these factors regulate RNA. Our laboratory has
recently generated a new platform for cell-specific Crosslinked Immunoprecipitation (CLIP) of RBPs in the living
brain of mice (cTag-CLIP), which has furthered our understanding of the cell-specific regulatory functions of
RBPs; however, this technology is limited to looking at steady state RNA regulation. Here we described a novel
approach to uncover the role of neuronal RBP-mediated RNA regulation in the context of synaptic plasticity. This
methodology, termed opto-CLIP, will combine the cell type-specific resolution afforded by cTag-CLIP with the
unprecedented precision of optogenetics to achieve non-invasive optical control of specific neurons. Once
established, we will increase the cellular resolution by performing opto-CLIP in distinct subcellular compartments
to assess local RNA regulation associated with neuronal function. This study will further our understanding of
RBP-mediated RNA regulation, enhance our knowledge of the role of RNA metabolism in synaptic plasticity, and
provide new insight into the pathological mechanisms underlying neurological disorders. In conclusion, I am
confident that my experience studying RNA biology, the Darnell lab's foundation in neuroscience and CLIP, and
the rich research environment at Rockefeller University will help me succeed in using optogenetics to study the
role of RBP-mediated RNA regulation in synaptic plasticity.
项目摘要
神经元具有高度专业化的结构和功能;它们的遗传信息通常位于很大的位置。
它们必须动态地改变突触,
蛋白质组对神经活动的反应。这些挑战表明,神经元已经进化出独特的调节机制,
满足功能需求。不同细胞类型的DNA的一致性表明,
遗传信息的展开和处理是细胞多样性的基础。在这种情况下,仔细检查
RNA代谢的调节,前mRNA基因拷贝如何被选择性剪接和多腺苷酸化,编辑,
本地化和规范化,将提供一个新的途径来理解复杂的过程,
作为学习和记忆基础的突触可塑性。这一概念促使分子神经科学家们寻找
定位和调节突触RNA的因子。我们才刚刚开始编制这些关键要素的清单
调节剂,如RNA结合蛋白(RBP),特别是在海马神经元的突触中,
这些因子与记忆有关,迄今为止,人们对这些因子如何调节RNA知之甚少。本实验室
最近产生了一个新的平台,细胞特异性交联免疫沉淀(CLIP)的RBP在生活中
小鼠脑(cTag-CLIP),这进一步加深了我们对细胞特异性调节功能的理解,
然而,这项技术仅限于观察稳态RNA调控。这里我们描述了一部小说
揭示神经元RBP介导的RNA调节在突触可塑性中的作用的方法。这
一种称为opto-CLIP的方法将联合收割机结合cTag-CLIP提供的细胞类型特异性分辨率与
光遗传学前所未有的精确度,以实现特定神经元的非侵入性光学控制。一旦
我们将通过在不同的亚细胞区室中进行opto-CLIP来提高细胞分辨率
以评估与神经元功能相关的局部RNA调节。这项研究将进一步加深我们对
RBP介导的RNA调节,增强了我们对RNA代谢在突触可塑性中的作用的认识,
为神经系统疾病的病理机制提供了新的见解。总之,我
我相信,我学习RNA生物学的经验,达内尔实验室在神经科学和CLIP方面的基础,
洛克菲勒大学丰富的研究环境将帮助我成功地利用光遗传学来研究
RBP介导的RNA调节在突触可塑性中的作用。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Ruth A Singer其他文献
Long noncoding RNAs are critical regulators of pancreatic islet development and function
- DOI:
10.7916/d8-nnax-mb40 - 发表时间:
2019 - 期刊:
- 影响因子:0
- 作者:
Ruth A Singer - 通讯作者:
Ruth A Singer
Ruth A Singer的其他文献
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{{ truncateString('Ruth A Singer', 18)}}的其他基金
Shedding light on the role of RNA binding protein-mediated RNA regulation in synaptic plasticity
揭示 RNA 结合蛋白介导的 RNA 调节在突触可塑性中的作用
- 批准号:
10456082 - 财政年份:2021
- 资助金额:
$ 6.64万 - 项目类别:
The role of long noncoding RNAs in regulating pancreas development and function
长链非编码RNA在调节胰腺发育和功能中的作用
- 批准号:
9150295 - 财政年份:2016
- 资助金额:
$ 6.64万 - 项目类别:
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