DNA forms conformational states beyond the right-handed double helix; however, the functional relevance of these noncanonical structures in the brain remains unknown. Here we show that, in the prefrontal cortex of mice, the formation of one such structure, Z-DNA, is involved in the regulation of extinction memory. Z-DNA is formed during fear learning and reduced during extinction learning, which is mediated, in part, by a direct interaction between Z-DNA and the RNA-editing enzyme Adar1. Adar1 binds to Z-DNA during fear extinction learning, which leads to a reduction in Z-DNA at sites where Adar1 is recruited. Knockdown of Adar1 leads to an inability to modify a previously acquired fear memory and blocks activity-dependent changes in DNA structure and RNA state-effects that are fully rescued by the introduction of full-length Adar1. These findings suggest a new mechanism of learning-induced gene regulation that is dependent on proteins that recognize alternate DNA structure states, which are required for memory flexibility.

中文翻译：

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RNA 编辑酶 Adar1 对小鼠前额叶皮层中 Z-DNA 的动态调节是消除恐惧所必需的。

DNA 在右手双螺旋之外形成构象状态；然而，大脑中这些非规范结构的功能相关性仍然未知。在这里，我们表明，在小鼠的前额叶皮层中，一种这样的结构 Z-DNA 的形成与消退记忆的调节有关。Z-DNA 在恐惧学习过程中形成，在消退学习过程中减少，这部分是由 Z-DNA 和 RNA 编辑酶 Adar1 之间的直接相互作用介导的。在恐惧消退学习期间，Adar1 与 Z-DNA 结合，这导致招募 Adar1 的位点的 Z-DNA 减少。Adar1 的敲低导致无法修改先前获得的恐惧记忆并阻止 DNA 结构和 RNA 状态效应的活动依赖性变化，这些变化通过引入全长 Adar1 完全挽救。