Post-Transcriptional Gene Regulation In Normal And Diseased Neurons

Description

Trisomy 21 (T21, a.k.a. Down syndrome) is the most common genetic form of intellectual disability, and iscaused by inheriting three copies of chromosome 21 (HSA21). Animal models of T21 have demonstrated anumber of synaptic aberrations. Accumulating evidence indicates that the 3' untranslated region (3'UTR) ofmRNA plays important roles in mRNA metabolism in neurons, including mRNA stability, translation, andlocalization. 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'UTRsare much longer than those in other cell types, adding another layer of post-transcriptional gene regulation inneuronal cells. However, little is known about the role of 3'UTR in the etiology of T21, and how APA isregulated 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.
StatusFinished
Effective start/end date2/1/171/31/19

Funding

  • National Institutes of Health (NIH)

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3' Untranslated Regions
Neurons
Polyadenylation
RNA-Binding Proteins
Genes
Neurogenesis
Down Syndrome
MicroRNAs
Chromosomes, Human, Pair 21
Neuronal Plasticity
RNA Stability
Protein Biosynthesis
Intellectual Disability
Protein Isoforms
Animal Models
Messenger RNA