Editors' ChoiceSynaptic Plasticity

Memorable microRNA

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Sci. Signal.  29 Sep 2009:
Vol. 2, Issue 90, pp. ec317
DOI: 10.1126/scisignal.290ec317

Short inhibitory RNAs (~22 nucleotides) called microRNAs (miRs) provide a layer of regulation at the level of mRNAs to influence differentiation, metabolism, and proliferation. Now Rajasethupathy et al. have identified the microRNA miR-124 as a negative regulator of a form of plasticity in Aplysia, the long-term facilitation (LTF) that occurs between sensory neurons and motor neurons (see commentary by Fischbach and Carew). By screening small RNA cDNA libraries, the authors identified 170 miRNAs in Aplysia, of which all but 13 were conserved in orthologs. Nine miRNAs were enriched in Aplysia brain and in a culture system of an intact sensory neuron–motor neuron circuit; miR-124 was one of several brain-enriched miRNAs that was present only in the sensory neuron. Repeated exposure of the coculture circuit to serotonin, which produces LTF, triggered a reduction in the abundance of miR-124, without altering the abundance of the precursor miRNA, whereas a single serotonin exposure, which does not produce LTF, did not change the abundance of miR-124. Treatments that increased miR-124 or decreased miR-124 inhibited or enhanced LTF, respectively. The decrease in miR-124 abundance in response to repeated application of serotonin was blocked by inhibitors of mitogen-activated protein kinase signaling but not by inhibitors of protein kinase A, protein kinase C, or of the proteasome. Abundance of the transcription factor CREB1, which is implicated in long-term plasticity, was increased when miR-124 was inhibited and a miR-124 consensus site in the 3'-untranslated region of the CREB1 transcript conferred miR-124 regulation in a reporter assay. This work characterizes the role of a specific microRNA in synaptic plasticity from the upstream regulator of the specific microRNA to its downstream targets and expands the roles associated with miR-124 beyond specification of neuronal identity.

P. Rajasethupathy, F. Fiumara, R. Sheridan, D. Betel. S. V. Puthanveettil, J. J. Russo, C. Sander, T. Tuschl, E. Kandel, Characterization of small RNAs in Aplysia reveals a role for miR-124 in constraining synaptic plasticity through CREB. Neuron 63, 803–817 (2009). [PubMed]

S. J. Fischbach, T. J. Carew, MicroRNAs in memory processing. Neuron 63, 714–716 (2009). [PubMed]