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

作者：Rajasethupathy Priyamvada; Antonov Igor; Sheridan Robert; Frey Sebastian; Sander Chris; Tuschl Thomas^*; Kandel Eric R

来源：Cell, 2012, 149(3): 693-707.

DOI：10.1016/j.cell.2012.02.057

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.

• 出版日期2012-4-27