RT Journal
A1 Kapoor, Utkarsh
A1 Licht, Konstantin
A1 Amman, Fabian
A1 Jakobi, Tobias
A1 Martin, David
A1 Dieterich, Christoph
A1 Jantsch, Michael
T1 ADAR-deficiency perturbs the global splicing landscape in mouse tissues
JF Genome Research 
JO Genome Research 
YR 2020 
FD July 29 
DO 10.1101/gr.256933.119 
SP gr.256933.119 
UL http://genome.cshlp.org/content/early/2020/07/29/gr.256933.119.abstract 
AB Adenosine to inosine RNA-editing and pre-mRNA splicing largely occur co-transcriptionally 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 towards splicing being regulated by editing in a tissue-specific manner.