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A role for neuronal piRNAs in the epigenetic control of memory-related synaptic plasticity |
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| Authors: | Rajasethupathy Priyamvada Antonov Igor Sheridan Robert Frey Sebastian Sander Chris Tuschl Thomas Kandel Eric R |
| Affiliation: | 1 Department of Neuroscience, Columbia University, New York, NY 10032, USA 2 Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA 3 Kavli Institute for Brain Sciences, Columbia University, New York, NY 10032, USA 4 Computational and Systems Biology Center, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA 5 Laboratory of RNA Molecular Biology, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065, 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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