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

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

doi:10.1016/j.celrep.2022.110546

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.

Authors

Wei Wei¹, Qiongyi Zhao², Ziqi Wang², Wei-Siang Liau², Dean Basic², Haobin Ren², Paul R Marshall², Esmi L Zajaczkowski², Laura J Leighton², Sachithrani U Madugalle², Mason Musgrove², Ambika Periyakaruppiah², Jichun Shi³, Jianjian Zhang⁴, John S Mattick⁵, Timothy R Mercer⁶, Robert C Spitale⁷, Xiang Li⁸, Timothy W Bredy⁹

Affiliations

¹ Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China; Brain Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China; Medical Research Institute, Wuhan University, Wuhan, China. Electronic address: [email protected].
² Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Australia.
³ Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China; Brain Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
⁴ Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
⁵ School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, Australia.
⁶ Australian Institute of Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia.
⁷ Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, USA.
⁸ Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China; Brain Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China; Medical Research Institute, Wuhan University, Wuhan, China.
⁹ Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Australia. Electronic address: [email protected].

Abstract

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

Substances

14-3-3 Proteins
RNA, Long Noncoding

Abstract

Publication types

MeSH terms

Substances

Grants and funding