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.
PROJECT NARRITIVE 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). In this project we plan to examine how transcript isoforms are expressed during neurogenesis of normal and T21 cells and how post-transcriptional gene regulation is executed in normal and T21 neurons.
| McGowan, Heather; Mirabella, Vincent R; Hamod, Aula et al. (2018) hsa-let-7c miRNA Regulates Synaptic and Neuronal Function in Human Neurons. Front Synaptic Neurosci 10:19 |
| Fontes, Mariana M; Guvenek, Aysegul; Kawaguchi, Riki et al. (2017) Activity-Dependent Regulation of Alternative Cleavage and Polyadenylation During Hippocampal Long-Term Potentiation. Sci Rep 7:17377 |
