Authors: | Rajasethupathy, P.; Antonov, I.; Sheridan, R.; Frey, S.; Sander, C.; Tuschl, T.; Kandel, E. R. |
Article 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. © 2012 Elsevier Inc. |
Keywords: | controlled study; methylation; promoter region; nonhuman; sensitivity analysis; animal cell; phenotype; animals; animal tissue; nerve tissue proteins; rna, small interfering; neurons; gene expression regulation; molecular sequence data; epigenetics; cpg island; nerve cell plasticity; base sequence; gene control; gene regulatory network; memory; nuclear localization signal; activating transcription factor 4; piwi interacting rna; biogenesis; serotonin; aplysia; neuronal plasticity; synapses; epigenomics; germline micronucleus |
Journal Title: | Cell |
Volume: | 149 |
Issue: | 3 |
ISSN: | 0092-8674 |
Publisher: | Cell Press |
Date Published: | 2012-04-27 |
Start Page: | 693 |
End Page: | 707 |
Language: | English |
DOI: | 10.1016/j.cell.2012.02.057 |
PROVIDER: | scopus |
PUBMED: | 22541438 |
PMCID: | PMC3442366 |
DOI/URL: | |
Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 4 June 2012" - "CODEN: CELLB" - "Source: Scopus" |