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一种长链非编码eRNA形成R环以塑造情绪体验诱导的行为适应。

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

作者信息

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

机构信息

Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.

Medical Scientist Training Program, Medical University of South Carolina, Charleston, SC, USA.

出版信息

Science. 2024 Dec 13;386(6727):1282-1289. doi: 10.1126/science.adp1562. Epub 2024 Dec 12.

DOI:10.1126/science.adp1562
PMID:39666799
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12071198/
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 (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 gene induction. Furthermore, in mouse models, 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.

摘要

情感体验常常引发神经可塑性，这种可塑性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。这些适应性变化部分由即时早期反应基因（如神经元PAS结构域蛋白4）的经验依赖性激活所支持。在这里，我们表明，从一个活性敏感增强子转录而来的保守长链非编码增强子RNA（lnc-eRNA）产生DNA:RNA杂交R环结构，该结构支持增强子与近端启动子之间的三维染色质环化以及快速的基因诱导。此外，在小鼠模型中，lnc-eRNA及其R环是慢性心理社会应激或可卡因暴露所产生的行为适应性发展所必需的，这揭示了这种调节机制在情感体验传递中的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e301/12071198/dd3425e9bfcd/nihms-2073994-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e301/12071198/9cc6ebf4a9a8/nihms-2073994-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e301/12071198/e290c7d2ebd8/nihms-2073994-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e301/12071198/3bab4a308fdd/nihms-2073994-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e301/12071198/f4296ca5ddea/nihms-2073994-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e301/12071198/dd3425e9bfcd/nihms-2073994-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e301/12071198/9cc6ebf4a9a8/nihms-2073994-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e301/12071198/e290c7d2ebd8/nihms-2073994-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e301/12071198/3bab4a308fdd/nihms-2073994-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e301/12071198/f4296ca5ddea/nihms-2073994-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e301/12071198/dd3425e9bfcd/nihms-2073994-f0005.jpg

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Dual roles of R-loops in the formation and processing of programmed DNA double-strand breaks during meiosis.R环在减数分裂过程中程序性DNA双链断裂形成和加工中的双重作用。
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A NPAS4-NuA4 complex couples synaptic activity to DNA repair.一个 NPAS4-NuA4 复合物将突触活动与 DNA 修复联系起来。
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NPAS4 in the medial prefrontal cortex mediates chronic social defeat stress-induced anhedonia-like behavior and reductions in excitatory synapses.内侧前额叶皮层中的 NPAS4 介导慢性社会挫败应激引起的快感缺失样行为和兴奋性突触减少。
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