A high resolution A-to-I editing map in the mouse identifies editing events controlled by pre-mRNA splicing.
Adenosine Deaminase
/ metabolism
Alternative Splicing
Animals
Brain
/ metabolism
Chromosome Mapping
Gene Expression Profiling
Mice
Organ Specificity
RNA Editing
RNA Precursors
/ genetics
RNA-Binding Proteins
/ metabolism
Repetitive Sequences, Nucleic Acid
Sequence Analysis, RNA
/ methods
Transcription, Genetic
Journal
Genome research
ISSN: 1549-5469
Titre abrégé: Genome Res
Pays: United States
ID NLM: 9518021
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
05
08
2018
accepted:
25
07
2019
pubmed:
21
8
2019
medline:
25
2
2020
entrez:
21
8
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31427386
pii: gr.242636.118
doi: 10.1101/gr.242636.118
pmc: PMC6724681
doi:
Substances chimiques
RNA Precursors
0
RNA-Binding Proteins
0
ADAR1 protein, mouse
EC 3.5.4.4
ADAR2 protein, mouse
EC 3.5.4.4
Adenosine Deaminase
EC 3.5.4.4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1453-1463Subventions
Organisme : Austrian Science Fund FWF
ID : P 26882
Pays : Austria
Informations de copyright
© 2019 Licht et al.; Published by Cold Spring Harbor Laboratory Press.
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