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

• 成果类型: Article
• 署名作者: Akiki, Rose Marie; Cornbrooks, Rebecca G.; Magami, Kosuke; Greige, Alain; Snyder, Kirsten K.; Wood, Daniel J.; Herrington, Mary Claire; Mace, Philip; Blidy, Kyle; Koike, Nobuya; Berto, Stefano; Cowan, Christopher W.; Taniguchi, Makoto
• 署名单位: Medical University of South Carolina; Medical University of South Carolina; Kyoto Prefectural University of Medicine
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10354
• DOI: 10.1126/science.adp1562
• 发表日期: 2024-12-01
• 页码: 1282-1289
• 关键词: nucleus-accumbens; neuronal-activity; gene-expression; social defeat; rna; npas4; transcription; reveals; program; binding

摘要

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 Npas4 (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 Npas4 gene induction. Furthermore, in mouse models, Npas4 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.