ADAR-deficiency perturbs the global splicing landscape in mouse tissues
- Utkarsh Kapoor1,4,
- Konstantin Licht1,4,
- Fabian Amman1,2,
- Tobias Jakobi3,
- David Martin1,
- Christoph Dieterich3 and
- Michael F. Jantsch1
- 1Center of Anatomy and Cell Biology, Department of Cell and Developmental Biology, Medical University of Vienna, A-1090 Vienna, Austria;
- 2Institute of Theoretical Biochemistry, University of Vienna, A-1090 Vienna, Austria;
- 3Department of Internal Medicine III and Klaus Tschira Institute for Computational Cardiology, Section of Bioinformatics and Systems Cardiology, University Hospital, D-96120 Heidelberg, Germany
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↵4 These authors contributed equally to this work.
Abstract
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.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.256933.119.
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Freely available online through the Genome Research Open Access option.
- Received September 9, 2019.
- Accepted July 10, 2020.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
