2020年5月4日，澳大利亚昆士兰大学Timothy W. Bredy团队在《自然-神经科学》杂志发表论文。他们研究发现在小鼠前额叶皮层RNA编辑酶Adar1对Z-DNA的动态调控是消除恐惧所必需的。

在本研究中，研究人员发现在小鼠的前额叶皮层中，一种非右手双螺旋DNA-Z-DNA的形成与调控记忆消除有关。Z-DNA在恐惧学习过程中形成，而在消退学习过程中减少；Z-DNA与RNA编辑酶Adar1之间的直接相互作用介导了此过程。

在恐惧消除过程中，Adar1与Z-DNA结合，从而导致招募到Adar1位点的Z-DNA减少。Adar1敲低无法消除先前获得的恐惧记忆并阻断了DNA结构和RNA状态的活动依赖性变化；而引入全长Adar1则可以完全挽救这种缺陷。

这些发现揭示了学习诱导基因调控的新机制，该机制依赖于识别替代性DNA结构的蛋白质，而这正是记忆灵活性所必需的。

研究人员表示，DNA可形成除右手双螺旋外的其它构象；然而，这些非经典结构在大脑中的相关功能仍然未知。

附：英文原文

Title: Dynamic regulation of Z-DNA in the mouse prefrontal cortex by the RNA-editing enzyme Adar1 is required for fear extinction

Author: Paul R. Marshall, Qiongyi Zhao, Xiang Li, Wei Wei, Ambika Periyakaruppiah, Esmi L. Zajaczkowski, Laura J. Leighton, Sachithrani U. Madugalle, Dean Basic, Ziqi Wang, Jiayu Yin, Wei-Siang Liau, Ankita Gupte, Carl R. Walkley, Timothy W. Bredy

Issue&Volume: 2020-05-04

Abstract: 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.

DOI: 10.1038/s41593-020-0627-5

Source: https://www.nature.com/articles/s41593-020-0627-5