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Cell. 2012 Apr 27;149(3):693-707. doi: 10.1016/j.cell.2012.02.057.

A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity.

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1
Department of Neuroscience, Columbia University, New York, NY 10032, USA.

Abstract

Small RNA-mediated gene regulation during development causes long-lasting changes in cellular phenotypes. To determine whether small RNAs of the adult brain can regulate memory storage, a process that requires stable and long-lasting changes in the functional state of neurons, we generated small RNA libraries from the Aplysia CNS. In these libraries, we discovered an unexpectedly abundant expression of a 28 nucleotide sized class of piRNAs in brain, which had been thought to be germline specific. These piRNAs have unique biogenesis patterns, predominant nuclear localization, and robust sensitivity to serotonin, a modulatory transmitter that is important for memory. We find that the Piwi/piRNA complex facilitates serotonin-dependent methylation of a conserved CpG island in the promoter of CREB2, the major inhibitory constraint of memory in Aplysia, leading to enhanced long-term synaptic facilitation. These findings provide a small RNA-mediated gene regulatory mechanism for establishing stable long-term changes in neurons for the persistence of memory.

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PMID:
22541438
PMCID:
PMC3442366
DOI:
10.1016/j.cell.2012.02.057
[Indexed for MEDLINE]
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