ADAR-deficiency perturbs the global splicing landscape in mouse tissues

Utkarsh Kapoor, Konstantin Licht, Fabian Amman, Tobias Jakobi, David Martin, Christoph Dieterich, Michael F. Jantsch

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 Πof 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.

Original languageEnglish (US)
Pages (from-to)1107-1118
Number of pages12
JournalGenome Research
Volume30
Issue number8
DOIs
StatePublished - Jul 29 2020
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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