miRNAs regulate protein synthesis by suppressing translation or destabilizing mRNAs. Their role in the development and function of the nervous system is not well understood. In this year, we identified several miRNAs that regulates the development and function of synapses in the hippocampus. We found that expression of these miRNAs is regulated during the period of active synaptogenesis. We also searched for target mRNAs that are regulated by miRNAs. We have identified respective mRNA targets for these miRNAs and demonstrated that the expression level of target mRNAs inversely correlates with that of the miRNA. In addition, by using overexpression and knockdown approaches, we show that the regulation of miRNAs on synapse development is mediated by their target mRNAs. These findings indicate that miRNAs play important roles in the development of synapses.

Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2011
Total Cost
$619,295
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
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Hu, Zhonghua; Li, Zheng (2017) miRNAs in synapse development and synaptic plasticity. Curr Opin Neurobiol 45:24-31
Shen, Hongmei; Li, Zheng (2016) miRNAs in NMDA receptor-dependent synaptic plasticity and psychiatric disorders. Clin Sci (Lond) 130:1137-46
Gu, Qin-Hua; Yu, Danni; Hu, Zhonghua et al. (2015) miR-26a and miR-384-5p are required for LTP maintenance and spine enlargement. Nat Commun 6:6789
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Hu, Zhonghua; Yu, Danni; Almeida-Suhett, Camila et al. (2012) Expression of miRNAs and their cooperative regulation of the pathophysiology in traumatic brain injury. PLoS One 7:e39357
Jiao, Song; Li, Zheng (2011) Nonapoptotic function of BAD and BAX in long-term depression of synaptic transmission. Neuron 70:758-72
Cleland, M M; Norris, K L; Karbowski, M et al. (2011) Bcl-2 family interaction with the mitochondrial morphogenesis machinery. Cell Death Differ 18:235-47
Li, Zheng; Jo, Jihoon; Jia, Jie-Min et al. (2010) Caspase-3 activation via mitochondria is required for long-term depression and AMPA receptor internalization. Cell 141:859-71