Faculty of Biology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel.
Medical Sciences Program, Indiana University, Bloomington, IN 47405, USA.
Cell Rep. 2019 Apr 23;27(4):1244-1253.e4. doi: 10.1016/j.celrep.2019.03.095.
A-to-I RNA editing, catalyzed by ADAR proteins, is widespread in eukaryotic transcriptomes. Studies showed that, in C. elegans, ADR-2 can actively deaminate dsRNA, whereas ADR-1 cannot. Therefore, we set out to study the effect of each of the ADAR genes on the RNA editing process. We performed comprehensive phenotypic, transcriptomics, proteomics, and RNA binding screens on worms mutated in a single ADAR gene. We found that ADR-1 mutants exhibit more-severe phenotypes than ADR-2, and some of them are a result of non-editing functions of ADR-1. We also show that ADR-1 significantly binds edited genes and regulates mRNA expression, whereas the effect on protein levels is minor. In addition, ADR-1 primarily promotes editing by ADR-2 at the L4 stage of development. Our results suggest that ADR-1 has a significant role in the RNA editing process and in altering editing levels that affect RNA expression; loss of ADR-1 results in severe phenotypes.
A-to-I RNA 编辑由 ADAR 蛋白催化，在真核转录组中广泛存在。研究表明，在 C. elegans 中，ADR-2 可以主动使 dsRNA 脱氨，而 ADR-1 则不能。因此，我们着手研究每个 ADAR 基因对 RNA 编辑过程的影响。我们对单个 ADAR 基因突变的蠕虫进行了全面的表型、转录组学、蛋白质组学和 RNA 结合筛选。我们发现 ADR-1 突变体比 ADR-2 表现出更严重的表型，其中一些是 ADR-1 的非编辑功能的结果。我们还表明，ADR-1 显著结合编辑基因并调节 mRNA 表达，而对蛋白质水平的影响较小。此外，ADR-1 主要在发育的 L4 阶段促进 ADR-2 的编辑。我们的结果表明，ADR-1 在 RNA 编辑过程中以及在改变影响 RNA 表达的编辑水平方面起着重要作用；ADR-1 的缺失会导致严重的表型。
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