title: A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity.
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.
authors.affiliation: Department of Neuroscience, Columbia University, New York, NY 10032, USA.
authors.forename: Priyamvada
authors.initials: P
authors.lastname: Rajasethupathy
authors.forename: Igor
authors.initials: I
authors.lastname: Antonov
authors.forename: Robert
authors.initials: R
authors.lastname: Sheridan
authors.forename: Sebastian
authors.initials: S
authors.lastname: Frey
authors.forename: Chris
authors.initials: C
authors.lastname: Sander
authors.forename: Thomas
authors.initials: T
authors.lastname: Tuschl
authors.forename: Eric R
authors.initials: ER
authors.lastname: Kandel
mesh_terms: D000818:Animals; D001048:Aplysia / Q000378:metabolism; D001483:Base Sequence; D057890:Epigenomics; D005786:Gene Expression Regulation; D006801:Humans; D008568:Memory; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology*; D034741:RNA, Small Interfering / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering