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：
ZHIPING P. PANG
金额：
$ 23.85万
依托单位：
RBHS-NEW JERSEY MEDICAL SCHOOL
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：
https://reporter.nih.gov/project-details/9316002
关键词：
3&apos Untranslated Regions Address Animal Model Bioinformatics Biological Cell Differentiation process Cell Fractionation Cell Line Cells Chromosomes, Human, Pair 21 Code Cytoplasm Development Disease Down Syndrome Elements Etiology Gene Expression Gene Expression Regulation Genes Genetic Genetic Transcription Genomics Human In Vitro Individual Inherited Intellectual functioning disability Maintenance Messenger RNA Metabolism Methods MicroRNAs Modeling Neurites Neurobiology Neurons Patients Peripheral Nervous System Play Pluripotent Stem Cells Polyadenylation Polyribosomes Post-Transcriptional Regulation Primates Process Prosencephalon Protein Isoforms Proteins RNA Binding RNA Processing RNA-Binding Proteins Regulation Reproducibility Research Research Personnel Role Site Stem Cell Research Synapses Techniques Technology Time Transcript Translations Untranslated Regions Work cell type deep sequencing differential expression excitatory neuron induced pluripotent stem cell interdisciplinary approach mRNA Stability nerve stem cell neurogenesis neuropsychiatric disorder synaptic function synaptogenesis transcription factor transcriptome 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.

项目摘要三体术21（T21，又称唐氏综合症）是智障的最常见遗传形式，是遗传了三个染色体21（HSA21）的副本引起的。 T21的动物模型已证明突触畸变的数量。积累的证据表明3'未翻译区域（3'UTR） mRNA在神经元中的mRNA代谢中起重要作用，包括mRNA稳定性，翻译和本土化。 3'UTR是由microRNA（miRNA）靶向的顺式元件或由RNA-结合的温床结合蛋白（RBP）。 miRNA和RBP都涉及旋转生成，树突状树博化，和突触发生。有趣的是，由于替代裂解和聚腺苷酸化（APA），神经元3'UTRS 比其他细胞类型中的时间长得多，在神经元细胞。但是，对于3'UTR在T21病因中的作用以及APA的作用知之甚少在T21细胞的神经发生过程中受到调控，从未探索过。该项目的目标是1）检查在正常和T21细胞神经发生过程中如何表达3'UTR同工型； 2）如何发布转录调节是通过正常和T21神经元中的3'UTRS执行的。