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

Autor: Wei Wei, Qiongyi Zhao, Ziqi Wang, Wei-Siang Liau, Dean Basic, Haobin Ren, Paul R. Marshall, Esmi L. Zajaczkowski, Laura J. Leighton, Sachithrani U. Madugalle, Mason Musgrove, Ambika Periyakaruppiah, Jichun Shi, Jianjian Zhang, John S. Mattick, Timothy R. Mercer, Robert C. Spitale, Xiang Li, Timothy W. Bredy
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cell Reports, Vol 38, Iss 12, Pp 110546- (2022)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2022.110546
Popis: Summary: 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.
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