RT Journal
A1 Licht, Konstantin
A1 Kapoor, Utkarsh
A1 Amman, Fabian
A1 Picardi, Ernesto
A1 Martin, David
A1 Bajad, Prajakta
A1 Jantsch, Michael F.
T1 A high resolution A-to-I editing map in the mouse identifies editing events controlled by pre-mRNA splicing
JF Genome Research 
JO Genome Research 
YR 2019 
FD September 01 
VO 29 
IS 9 
SP 1453 
OP 1463 
DO 10.1101/gr.242636.118 
UL http://genome.cshlp.org/content/29/9/1453.abstract 
AB Pre-mRNA-splicing and adenosine to inosine (A-to-I) RNA-editing occur mostly cotranscriptionally. During A-to-I editing, a genomically encoded adenosine is deaminated to inosine by adenosine deaminases acting on RNA (ADARs). Editing-competent stems are frequently formed between exons and introns. Consistently, studies using reporter assays have shown that splicing efficiency can affect editing levels. Here, we use Nascent-seq and identify ∼90,000 novel A-to-I editing events in the mouse brain transcriptome. Most novel sites are located in intronic regions. Unlike previously assumed, we show that both ADAR (ADAR1) and ADARB1 (ADAR2) can edit repeat elements and regular transcripts to the same extent. We find that inhibition of splicing primarily increases editing levels at hundreds of sites, suggesting that reduced splicing efficiency extends the exposure of intronic and exonic sequences to ADAR enzymes. Lack of splicing factors NOVA1 or NOVA2 changes global editing levels, demonstrating that alternative splicing factors can modulate RNA editing. Finally, we show that intron retention rates correlate with editing levels across different brain tissues. We therefore demonstrate that splicing efficiency is a major factor controlling tissue-specific differences in editing levels.