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

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Science Pub Date : 2024-12-13 Epub Date: 2024-12-12 DOI:10.1126/science.adp1562

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

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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 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.

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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，包括与情绪障碍和药物使用障碍相关的不适应可塑性。这些适应性在一定程度上是由经验依赖性激活的即时早期反应基因（如 Npas4（神经元 PAS 结构域蛋白 4））支持的。在这里，我们发现了一种保守的长非编码增强子 RNA（lnc-eRNA），这种 RNA 从活性敏感的增强子转录而来，产生了 DNA:RNA 混合 R 循环结构，支持增强子和近端启动子之间的三维染色质循环以及 Npas4 基因的快速诱导。此外，在小鼠模型中，Npas4 lnc-eRNA 及其 R 环是慢性社会心理压力或可卡因暴露所产生的行为适应性发展所必需的，揭示了这种调控机制在情感体验传递中的潜在作用。

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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