TY - JOUR A1 - Kapoor, Utkarsh A1 - Licht, Konstantin A1 - Amman, Fabian A1 - Jakobi, Tobias A1 - Martin, David A1 - Dieterich, Christoph A1 - Jantsch, Michael F. T1 - ADAR-deficiency perturbs the global splicing landscape in mouse tissues Y1 - 2020/08/01 JF - Genome Research JO - Genome Research SP - 1107 EP - 1118 DO - 10.1101/gr.256933.119 VL - 30 IS - 8 UR - http://genome.cshlp.org/content/30/8/1107.abstract N2 - 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. ER -