Adenosine-to-inosine RNA editing and pre-mRNA splicing largely occur cotranscriptionally and influence each other. Here, we use mice deficient in either one of the two editing enzymes ADAR (ADAR1) or ADARB1 (ADAR2) to determine the transcriptome-wide impact of RNA editing on splicing across different tissues. We find that ADAR has a 100× higher impact on splicing than ADARB1, although both enzymes target a similar number of substrates with a large common overlap. Consistently, differentially spliced regions frequently harbor ADAR editing sites. Moreover, catalytically dead ADAR also impacts splicing, demonstrating that RNA binding of ADAR affects splicing. In contrast, ADARB1 editing sites are found enriched 5′ of differentially spliced regions. Several of these ADARB1-mediated editing events change splice consensus sequences, therefore strongly influencing splicing of some mRNAs. A significant overlap between differentially edited and differentially spliced sites suggests evolutionary selection toward splicing being regulated by editing in a tissue-specific manner.

中文翻译：

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ADAR 缺陷扰乱了小鼠组织中的全球剪接环境。

腺苷到肌苷 RNA 编辑和前 mRNA 剪接在很大程度上发生在共转录中并相互影响。在这里，我们使用缺乏两种编辑酶 ADAR (ADAR1) 或 ADARB1 (ADAR2) 之一的小鼠来确定 RNA 编辑对跨不同组织剪接的转录组范围的影响。我们发现 ADAR 对剪接的影响比 ADARB1 高 100 倍，尽管这两种酶都针对相似数量的底物，并且有很大的共同重叠。一致地，差异剪接区域经常包含 ADAR 编辑位点。此外，催化死亡的 ADAR 也会影响剪接，这表明 ADAR 的 RNA 结合会影响剪接。相反，发现 ADARB1 编辑位点富集了 5' 的差异剪接区域。这些 ADARB1 介导的编辑事件中的一些改变了剪接共有序列，因此强烈影响一些mRNA的剪接。差异编辑和差异剪接位点之间的显着重叠表明，通过以组织特异性方式编辑来调节剪接的进化选择。