研究人员展示了一种保守的长非编码增强子RNA（lnc-eRNA）。该RNA由活动敏感型增强子转录产生，形成DNA:RNA杂交R环结构，支持增强子和邻近启动子之间的三维染色质环形化，并促进Npas4（神经PAS结构域蛋白4）基因的快速诱导。
此外，在小鼠模型中，Npas4 lnc-eRNA及其R环对于由慢性社会心理压力或可卡因暴露引起的行为适应性变化的产生是必需的，继而揭示了这种调控机制在情绪体验传递中的潜在作用。
据介绍，情绪体验常常引发神经可塑性，支持行为的适应性变化，包括与情绪障碍和物质使用障碍相关的非适应性可塑性。这些适应性变化部分由经验依赖性激活的即刻早期反应基因支持，例如Npas4。
附：英文原文
Title: A long noncoding eRNA forms R-loops to shape emotional experience–induced behavioral adaptation
Author: 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
Issue&Volume: 2024-12-13
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.
DOI: adp1562
Source: https://www.science.org/doi/10.1126/science.adp1562