Post-transcriptional gene regulation in normal and diseased neurons
正常和患病神经元的转录后基因调控
基本信息
- 批准号:9316002
- 负责人:
- 金额:$ 23.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-02-01 至 2019-01-31
- 项目状态:已结题
- 来源:
- 关键词:3&apos Untranslated RegionsAddressAnimal ModelBioinformaticsBiologicalCell Differentiation processCell FractionationCell LineCellsChromosomes, Human, Pair 21CodeCytoplasmDevelopmentDiseaseDown SyndromeElementsEtiologyGene ExpressionGene Expression RegulationGenesGeneticGenetic TranscriptionGenomicsHumanIn VitroIndividualInheritedIntellectual functioning disabilityMaintenanceMessenger RNAMetabolismMethodsMicroRNAsModelingNeuritesNeurobiologyNeuronsPatientsPeripheral Nervous SystemPlayPluripotent Stem CellsPolyadenylationPolyribosomesPost-Transcriptional RegulationPrimatesProcessProsencephalonProtein IsoformsProteinsRNA BindingRNA ProcessingRNA-Binding ProteinsRegulationReproducibilityResearchResearch PersonnelRoleSiteStem Cell ResearchSynapsesTechniquesTechnologyTimeTranscriptTranslationsUntranslated RegionsWorkcell typedeep sequencingdifferential expressionexcitatory neuroninduced pluripotent stem cellinterdisciplinary approachmRNA Stabilitynerve stem cellneurogenesisneuropsychiatric disordersynaptic functionsynaptogenesistranscription factortranscriptome sequencing
项目摘要
PROJECT SUMMARY
Trisomy 21 (T21, a.k.a. Down syndrome) is the most common genetic form of intellectual disability, and is
caused by inheriting three copies of chromosome 21 (HSA21). Animal models of T21 have demonstrated a
number of synaptic aberrations. Accumulating evidence indicates that the 3' untranslated region (3'UTR) of
mRNA plays important roles in mRNA metabolism in neurons, including mRNA stability, translation, and
localization. The 3'UTR is a hotbed for cis elements targeted by microRNAs (miRNAs) or bound by RNA-
binding proteins (RBPs). Both miRNAs and RBPs have been implicated in spinogenesis, dendritic arborization,
and synaptogenesis. Interestingly, owing to alternative cleavage and polyadenylation (APA), neuronal 3'UTRs
are much longer than those in other cell types, adding another layer of post-transcriptional gene regulation in
neuronal cells. However, little is known about the role of 3'UTR in the etiology of T21, and how APA is
regulated during neurogenesis of T21 cells has never been explored. The objectives of this project are to 1)
examine how 3'UTR isoforms are expressed during neurogenesis of normal and T21 cells; and 2) how post-
transcriptional regulation is executed via 3'UTRs in normal and T21 neurons.
项目摘要
21三体(T21,a.k.a.唐氏综合症)是智力残疾的最常见遗传形式,
遗传了三个21号染色体(HSA 21)。T21的动物模型已经证明了
突触畸变的数量。越来越多的证据表明,3'非翻译区(3' UTR)的基因可能是一个重要的基因。
mRNA在神经元的mRNA代谢中起重要作用,包括mRNA的稳定性、翻译和表达。
本地化3 'UTR是microRNA(miRNAs)靶向或RNA结合的顺式元件的温床。
结合蛋白(RBPs)。miRNA和RBP都与棘发生、树突状分支、
和突触发生。有趣的是,由于交替切割和多聚腺苷酸化(阿帕),神经元3 'UTR
比其他类型的细胞长得多,在细胞中增加了另一层转录后基因调控。
神经元细胞然而,关于3 'UTR在T21的病因学中的作用以及阿帕是如何在T21中表达的,
在T21细胞的神经发生过程中的调节从未被探索过。本项目的目标是:1)
检查3 'UTR同种型在正常和T21细胞的神经发生期间如何表达;和2)3' UTR同种型在神经发生后如何表达。
在正常和T21神经元中,转录调节通过3 'UTR执行。
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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{{ truncateString('ZHIPING P. PANG', 18)}}的其他基金
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能量平衡中枢 GLP-1 信号传导的突触和电路机制
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Synaptic and circuit mechanisms of central GLP-1 signaling in energy balance
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9217533 - 财政年份:2016
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Cellular and genomic mechanisms of the impact of ethanol on human neural model
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10613547 - 财政年份:2016
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