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

Cell. 2012 Apr 27;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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aplysia / metabolism
  • Base Sequence
  • Epigenomics*
  • Gene Expression Regulation
  • Humans
  • Memory*
  • Molecular Sequence Data
  • Nerve Tissue Proteins / metabolism
  • Neuronal Plasticity*
  • Neurons / physiology*
  • RNA, Small Interfering / metabolism*
  • Synapses / metabolism


  • Nerve Tissue Proteins
  • RNA, Small Interfering