A brain-specific microRNA regulates dendritic spine development.
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.
Schratt
Gerhard M
GM
Neurobiology Program, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Tuebing
Fabian
F
Nigh
Elizabeth A
EA
Kane
Christina G
CG
Sabatini
Mary E
ME
Kiebler
Michael
M
Greenberg
Michael E
ME
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D048430:Cell Shape; D049229:Dendritic Spines / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D054461:Lim Kinases; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D035683:MicroRNAs; D012333:RNA, Messenger; D011494:Protein Kinases; D054461:Lim Kinases; C515894:Limk1 protein, rat