ADRAM is an experience-dependent long noncoding RNA that drives fear extinction through a direct interaction with the chaperone protein 14-3-3

Cell Rep. 2022 Mar 22;38(12):110546. doi: 10.1016/j.celrep.2022.110546.


Here, we used RNA capture-seq to identify a large population of lncRNAs that are expressed in the infralimbic prefrontal cortex of adult male mice in response to fear-related learning. Combining these data with cell-type-specific ATAC-seq on neurons that had been selectively activated by fear extinction learning, we find inducible 434 lncRNAs that are derived from enhancer regions in the vicinity of protein-coding genes. In particular, we discover an experience-induced lncRNA we call ADRAM (activity-dependent lncRNA associated with memory) that acts as both a scaffold and a combinatorial guide to recruit the brain-enriched chaperone protein 14-3-3 to the promoter of the memory-associated immediate-early gene Nr4a2 and is required fear extinction memory. This study expands the lexicon of experience-dependent lncRNA activity in the brain and highlights enhancer-derived RNAs (eRNAs) as key players in the epigenomic regulation of gene expression associated with the formation of fear extinction memory.

Keywords: CP: Molecular Biology; CP: Neuroscience; chaperone; eRNA; fear extinction; long noncoding RNA; memory.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / genetics
  • 14-3-3 Proteins / metabolism
  • Animals
  • Extinction, Psychological / physiology
  • Fear* / physiology
  • Male
  • Mice
  • Prefrontal Cortex / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism


  • 14-3-3 Proteins
  • RNA, Long Noncoding