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Genome-wide identification and characterisation of tissue-specific RNA editing events in D. melanogaster and their potential role in regulating alternative splicing

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Item Type:Article
Title:Genome-wide identification and characterisation of tissue-specific RNA editing events in D. melanogaster and their potential role in regulating alternative splicing
Creators Name:Mazloomian, A. and Meyer, I.M.
Abstract:RNA editing is a widespread mechanism that plays a crucial role in diversifying gene products. Its abundance and importance in regulating cellular processes were revealed using new sequencing technologies. The majority of these editing events, however, cannot be associated with regulatory mechanisms. We use tissue-specific high-throughput libraries of D. melanogaster to study RNA editing. We introduce an analysis pipeline that utilises large input data and explicitly captures ADAR's requirement for double-stranded regions. It combines probabilistic and deterministic filters and can identify RNA editing events with a low estimated false positive rate. Analysing ten different tissue types, we predict 2879 editing sites and provide their detailed characterisation. Our analysis pipeline accurately distinguishes genuine editing sites from SNPs and sequencing and mapping artefacts. Our editing sites are three times more likely to occur in exons with multiple splicing acceptor/donor sites than in exons with unique splice sites (p-value < 2 10-15). Furthermore, we identify 244 edited regions where RNA editing and alternative splicing are likely to influence each other. For 96 out of these 244 regions, we find evolutionary evidence for conserved RNA secondary-structures near splice sites suggesting a potential regulatory mechanism where RNA editing may alter splicing patterns via changes in local RNA structure.
Keywords:ADAR, RNA Editing, RNA Secondary Structure, Alternative Splicing, Post-Transcriptional Regulation, Animals, Drosophila Melanogaster
Source:RNA Biology
ISSN:1547-6286
Publisher:Taylor & Francis (U.S.A)
Volume:12
Number:12
Page Range:1391-1401
Date:December 2015
Official Publication:https://doi.org/10.1080/15476286.2015.1107703
PubMed:View item in PubMed

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