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
Affiliations
Wei Wei
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; Corresponding author
Qiongyi Zhao
Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
Ziqi Wang
Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
Wei-Siang Liau
Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
Dean Basic
Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
Haobin Ren
Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
Paul R. Marshall
Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
Esmi L. Zajaczkowski
Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
Laura J. Leighton
Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
Sachithrani U. Madugalle
Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
Mason Musgrove
Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
Ambika Periyakaruppiah
Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Australia
Jichun Shi
Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China; Brain Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China
Jianjian Zhang
Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
John S. Mattick
School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, Australia
Timothy R. Mercer
Australian Institute of Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Australia
Robert C. Spitale
Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, USA
Xiang Li
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
Timothy W. Bredy
Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Australia; Corresponding author
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.
