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.

中文翻译：

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一个长的非编码 eRNA 形成 R 环来塑造情绪体验诱导的行为适应


情绪体验通常会唤起神经可塑性，从而支持行为的适应性变化，包括与情绪和物质使用障碍相关的适应不良可塑性。这些适应部分由即时早期反应基因的经验依赖性激活支持，例如 Npas4 （神经元 PAS 结构域蛋白 4）。在这里，我们展示了从活性敏感增强子转录而来的保守长非编码增强子 RNA （lnc-eRNA） 产生 DNA：RNA 杂交 R 环结构，该结构支持增强子和近端启动子之间的三维染色质环以及快速 Npas4 基因诱导。此外，在小鼠模型中，Npas4 lnc-eRNA 及其 R 环是慢性心理社会压力或可卡因暴露产生的行为适应发展所必需的，揭示了这种调节机制在情绪体验传递中的潜在作用。