ADAR proteins alter gene expression both by catalyzing adenosine (A) to inosine (I) RNA editing and binding to regulatory elements in target RNAs. Loss of ADARs affects neuronal function in all animals studied to date. Caenorhabditis elegans lacking ADARs exhibit reduced chemotaxis, but the targets responsible for this phenotype remain unknown. To identify critical neural ADAR targets in C. elegans, we performed an unbiased assessment of the effects of ADR-2, the only A-to-I editing enzyme in C. elegans, on the neural transcriptome. Development and implementation of publicly available software, SAILOR, identified 7361 A-to-I editing events across the neural transcriptome. Intersecting the neural editome with adr-2 associated gene expression changes, revealed an edited mRNA, clec-41, whose neural expression is dependent on deamination. Restoring clec-41 expression in adr-2 deficient neural cells rescued the chemotaxis defect, providing the first evidence that neuronal phenotypes of ADAR mutants can be caused by altered gene expression.

中文翻译：

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秀丽隐杆线虫神经编辑组揭示了适当趋化性所需的 ADAR 靶标 mRNA

ADAR 蛋白通过催化腺苷 (A) 到肌苷 (I) RNA 编辑以及与目标 RNA 中的调控元件结合来改变基因表达。ADAR 的缺失会影响迄今为止研究的所有动物的神经元功能。缺乏 ADAR 的秀丽隐杆线虫表现出降低的趋化性，但导致这种表型的目标仍然未知。为了确定秀丽隐杆线虫中的关键神经 ADAR 靶标，我们对 ADR-2（秀丽隐杆线虫中唯一的 A-to-I 编辑酶）对神经转录组的影响进行了公正评估。公开可用软件 SAILOR 的开发和实施确定了整个神经转录组中的 7361 个 A-to-I 编辑事件。将神经编辑组与 adr-2 相关基因表达变化相交，揭示了一个编辑过的 mRNA，clec-41，其神经表达依赖于脱氨基作用。