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miR-9 and miR-124 synergistically affect regulation of dendritic branching via the AKT/GSK3β pathway by targeting Rap2a

Xue, Q, Yu, C, Wang, Y, Liu, L, Zhang, K, Fang, C, Liu, F, Bian, G, Song, B, Yang, A, Ju, G and Wang, J 2016. miR-9 and miR-124 synergistically affect regulation of dendritic branching via the AKT/GSK3β pathway by targeting Rap2a. Scientific Reports 6 , 26781. 10.1038/srep26781

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Abstract

A single microRNA (miRNA) can regulate expression of multiple proteins, and expression of an individual protein may be controlled by numerous miRNAs. This regulatory pattern strongly suggests that synergistic effects of miRNAs play critical roles in regulating biological processes. miR-9 and miR-124, two of the most abundant miRNAs in the mammalian nervous system, have important functions in neuronal development. In this study, we identified the small GTP-binding protein Rap2a as a common target of both miR-9 and miR-124. miR-9 and miR-124 together, but neither miRNA alone, strongly suppressed Rap2a, thereby promoting neuronal differentiation of neural stem cells (NSCs) and dendritic branching of differentiated neurons. Rap2a also diminished the dendritic complexity of mature neurons by decreasing the levels of pAKT and pGSK3β. Our results reveal a novel pathway in which miR-9 and miR-124 synergistically repress expression of Rap2a to sustain homeostatic dendritic complexity during neuronal development and maturation.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Dentistry
Publisher: Nature Publishing Group: Open Access Journals - Option B / Nature Publishing Group
ISSN: 2045-2322
Date of First Compliant Deposit: 26 October 2017
Date of Acceptance: 6 May 2016
Last Modified: 02 Feb 2018 23:37
URI: http://orca.cf.ac.uk/id/eprint/105988

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