A Role for Neuronal piRNAs in the Epigenetic Control of Memory-Related Synaptic Plasticity

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• 作者：Priyamvada Rajasethupathy¹ ; Igor Antonov¹ ; Robert Sheridan⁴ ; Sebastian Frey⁵ ; Chris Sander⁴ ; Thomas Tuschl⁵ ; ^{ttuschl@rockefeller.edu} ; Eric  ; R. Kandel¹ ; ² ; ³ ; ^{erk5@columbia.edu}
• 刊名：Cell
• 出版年：2012
• 期刊代码：50_00928674
• 类别：med
• 出版时间：27 April, 2012
• 卷：149
• 期：3
• 页码：693-707
• 文件大小：1665 K

摘要

| Figures/TablesFigures/Tables | ReferencesReferences<h3 class="h3">Summaryh3>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.