Zinc Finger RNA-Binding Protein Zn72D Regulates ADAR-Mediated RNA Editing in Neurons.
Zinc Finger RNA-Binding Protein Zn72D Regulates ADAR-Mediated RNA Editing in Neurons.
复制标题
锌指 RNA 结合蛋白 Zn72D 调节神经元中 ADAR 介导的 RNA 编辑。
DOI：
10.1016/j.celrep.2020.107654
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发表时间：
2020
期刊：
影响因子：
8.8
通讯作者：
Li,JinBilly
中科院分区：
文献类型：
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作者：
Sapiro,AnneL;Freund,EmilyC;Restrepo,Lucas;Qiao,Huan-Huan;Bhate,Amruta;Li,Qin;Ni,Jian-Quan;Mosca,TimothyJ;Li,JinBilly
腺苷-肌苷RNA编辑由作用于RNA（阿达尔）酶的腺苷脱氨酶催化，改变由DNA编码的RNA序列。这些编辑事件是动态调节的，但在体内很少有已知的ADAR的反式调节子。在这里，我们通过果蝇基因敲除实验筛选RNA结合蛋白在编辑调节中的作用。我们确定锌指蛋白72 D（Zn 72 D）作为大脑中大多数编辑位点的编辑水平的调节剂。Zn 72 D既调节阿达尔蛋白水平，又以RNA依赖的方式与阿达尔相互作用，并且与阿达尔类似，Zn 72 D是维持适当的神经肌肉接头结构和果蝇运动性所必需的。此外，Zn 72 D在RNA编辑中的调节作用是保守的，因为Zn 72 D的哺乳动物同系物Zfr调节小鼠原代神经元中的编辑。在神经元中，Zn 72 D对阿达尔编辑的广泛和保守的调节维持着至关重要的编辑事件。
Adenosine-to-inosine RNA editing, catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes, alters RNA sequences from those encoded by DNA. These editing events are dynamically regulated, but fewtransregulators of ADARs are knownin vivo. Here, we screen RNA-binding proteins for roles in editing regulation with knockdown experiments in theDrosophilabrain. We identify zinc-finger protein at 72D (Zn72D) as a regulator of editing levels at a majority of editing sites in the brain. Zn72D both regulates ADAR protein levels and interacts with ADAR in an RNA-dependent fashion, and similar to ADAR, Zn72D is necessary to maintain proper neuromuscular junction architecture and fly mobility. Furthermore, Zn72D's regulatory role in RNA editing is conserved because the mammalian homolog of Zn72D, Zfr, regulates editing in mouse primary neurons. The broad and conserved regulation of ADAR editing by Zn72D in neurons sustains critically important editing events.