miRNA Contributes to Neuronal Morphogenesis

Science's STKE  15 Nov 2005:
Vol. 2005, Issue 310, pp. tw406
DOI: 10.1126/stke.3102005tw406

Using a genomic screen for genes regulated by cAMP-response element binding protein (CREB), Vo et al. identified the microRNA miR132 as a potential locus regulated by CREB. Brain-derived neurotrophic factor (BDNF) stimulated a persistent increase in the expression of the miR132 precursor and abundance of the mature miR132 in a CREB-dependent manner in cortical neurons. Overexpression of miR132 in primary cortical neurons increased neurite outgrowth (number of processes and their length), and treatment of the cells with antisense for miRNA132 attenuated neurite outgrowth. Cotransfection of p250GAP (a guanosine triphosphatase-activating protein for members of the Rac and Rho family of GTPases) and the miR132 precursor decreased the abundance of p250GAP relative to that in cells only transfected with p250GAP. Furthermore, using short-hairpin RNA (shRNA) to decrease 250GAP in cortical neurons, neurite outgrowth was increased. Thus, miRNAs can be added to the mediators of CREB-stimulated changes in neuronal morphology.

N. Vo, M. E. Klein, O. Varlamova, D. M. Keller, T. Yamamoto, R. H. Goodman, S. Impey, A cAMP-response element binding protein-induced microRNA regulates neuronal morphogenesis. Proc. Natl. Acad. Sci. U.S.A. 102, 16426-16431 (2005). [Abstract] [Full Text]