A long noncoding eRNA forms R-loops to shape emotional experience–induced behavioral adaptation

Emotional experiences often evoke neural plasticity that supports adaptive changes in behavior, including maladaptive plasticity associated with mood and substance use disorders. These adaptations are supported in part by experience-dependent activation of immediate-early response genes, such as <i>Npas4</i> (neuronal PAS domain protein 4). Here we show that a conserved long noncoding enhancer RNA (lnc-eRNA), transcribed from an activity-sensitive enhancer, produces DNA:RNA hybrid R-loop structures that support three-dimensional chromatin looping between enhancer and proximal promoter and rapid <i>Npas4</i> gene induction. Furthermore, in mouse models, <i>Npas4</i> lnc-eRNA and its R-loop are required for the development of behavioral adaptations produced by chronic psychosocial stress or cocaine exposure, revealing a potential role for this regulatory mechanism in the transmission of emotional experiences.

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Publication Details

Journal
Science
Published
2024-12-12
DOI
https://doi.org/10.1126/science.adp1562
Citations
28
Primary Topic
Cancer-related molecular mechanisms research
Type
article
Field-Weighted Citation Impact
7.98

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article

A long noncoding eRNA forms R-loops to shape emotional experience–induced behavioral adaptation

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28 citations
Science
Cancer-related molecular mechanisms research
7.98
article

A long noncoding eRNA forms R-loops to shape emotional experience–induced behavioral adaptation

Rose Marie Akiki, Nobuya Koike, Makoto Taniguchi, Christopher W. Cowan, Stefano Berto, Kirsten K. Snyder, Rebecca G Cornbrooks, Alain Greige, Daniel J. Wood, Kyle Blidy, Kosuke Magami, Mary Claire Herrington, Philip Mace
article en
28 citations

Abstract

Emotional experiences often evoke neural plasticity that supports adaptive changes in behavior, including maladaptive plasticity associated with mood and substance use disorders. These adaptations are supported in part by experience-dependent activation of immediate-early response genes, such as <i>Npas4</i> (neuronal PAS domain protein 4). Here we show that a conserved long noncoding enhancer RNA (lnc-eRNA), transcribed from an activity-sensitive enhancer, produces DNA:RNA hybrid R-loop structures that support three-dimensional chromatin looping between enhancer and proximal promoter and rapid <i>Npas4</i> gene induction. Furthermore, in mouse models, <i>Npas4</i> lnc-eRNA and its R-loop are required for the development of behavioral adaptations produced by chronic psychosocial stress or cocaine exposure, revealing a potential role for this regulatory mechanism in the transmission of emotional experiences.

ScienceVol. 386(6727)
Medical University of South Carolina (US), Kyoto Prefectural University of Medicine (JP)
Medical University of South Carolina, University of South Carolina, National Institutes of Health, South Carolina Clinical and Translational Research Institute, Medical University of South Carolina, National Institute of General Medical Sciences
Good health and well-being
Openalex Percentile: Top 2%
Cancer-related molecular mechanisms research
7.98
DOIOpen Access PDFOpenAlex
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