1. Neurobiology Program, Children's Hospital,
2. Department of Neurology,
3. Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA
4. Division of Neuronal Cell Biology, Center for Brain Research, Medical University of Vienna, A-1090 Vienna, Austria

Correspondence to: Michael E. Greenberg^1,2,3 Correspondence and requests for materials should be addressed to M.E.G. (Email: Michael.Greenberg@childrens.harvard.edu).

Abstract

MicroRNAs are small, non-coding RNAs that control the translation of target messenger RNAs, thereby regulating critical aspects of plant and animal development. In the mammalian nervous system, the spatiotemporal control of mRNA translation has an important role in synaptic development and plasticity. Although a number of microRNAs have been isolated from the mammalian brain, neither the specific microRNAs that regulate synapse function nor their target mRNAs have been identified. Here we show that a brain-specific microRNA, miR-134>, is localized to the synapto-dendritic compartment of rat hippocampal neurons and negatively regulates the size of dendritic spines—postsynaptic sites of excitatory synaptic transmission. This effect is mediated by miR-134 inhibition of the translation of an mRNA encoding a protein kinase, Limk1, that controls spine development. Exposure of neurons to extracellular stimuli such as brain-derived neurotrophic factor relieves miR-134 inhibition of Limk1 translation and in this way may contribute to synaptic development, maturation and/or plasticity.

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