Titel:
Exon-intron chain reconstruction of circular RNA using RNA-Seq
Beteiligte:
Metge, Franziska
[VerfasserIn]
Erschienen:
Cologne University: KUPS, 2018
Sprache:
Englisch
Entstehung:
Anmerkungen:
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Beschreibung:
Circular RNAs (circRNAs) are a class of RNA forming a covalently closed loop through back-splicing. A few well studied circRNAs indicate miRNA sponging and regulation of host gene transcription. CircRNAs can be identified in rRNA depleted RNA-Seq by detecting reads, which span a back-splice junction. CircRNA detection tools exist but none are able to summarize or characterize circRNAs. To perform accurate downstream analyses it is crucial to know the exact exon-intron structure of circRNAs. Here, I am presenting FUCHS and FUCHSdenovo to summarize circRNAs and reconstruct their exon-intron chain. In short: I developed a pipeline called FUCHS : FUll CHaracterization of circular RNA using RNA-Sequencing; that summarizes circRNAs, detects skipped exons, finds double-breakpoint fragments, generates coverage profiles, and clusters these profiles. I developed an additional module, FUCHSdenovo, to reconstruct the exon-intron structure based on linear-splice signals of back-spliced reads. I ran both programs on a dataset of young and old murine hearts and young and old murine livers. FUCHS revealed that heart circRNAs are less diverse but more abundant than liver circRNAs. From the obtained coverage profiles, I concluded that annotated gene models were not all matching the exon-intron structure of circRNAs. A de-novo reconstruction of circle structures using FUCHSdenovo showed a gain of information of 15%. Furthermore, FUCHSdenovo identified alternative splicing (AS) in 10% of circRNAs. Performing a differential motif enrichment analysis of the flanking introns of circRNAs with AS over circRNAs without AS identified FOXO as a potential transcription factor driving AS in circRNAs. Comparing the seed density of circRNAs and mRNAs showed that circRNAs were more densely populated with both. This suggests that circRNAs could form an additional layer in the gene-regulatory network by competing with their host genes for miRNA or RBP binding. https://github.com/dieterich-lab/FUCHS.git