Accurate identification of circRNA landscape and complexity reveals their pivotal roles in human oligodendroglia differentiation

dc.contributor.authorLi, Yangping
dc.contributor.authorWang, Feng
dc.contributor.authorTeng, Peng
dc.contributor.authorKu, Li
dc.contributor.authorChen, Li
dc.contributor.authorFeng, Yue
dc.contributor.authorYao, Bing
dc.contributor.departmentBiostatistics and Health Data Science, School of Medicineen_US
dc.date.accessioned2023-05-04T13:03:24Z
dc.date.available2023-05-04T13:03:24Z
dc.date.issued2022-02-07
dc.description.abstractBackground: Circular RNAs (circRNAs), a novel class of poorly conserved non-coding RNAs that regulate gene expression, are highly enriched in the human brain. Despite increasing discoveries of circRNA function in human neurons, the circRNA landscape and function in developing human oligodendroglia, the myelinating cells that govern neuronal conductance, remains unexplored. Meanwhile, improved experimental and computational tools for the accurate identification of circRNAs are needed. Results: We adopt a published experimental approach for circRNA enrichment and develop CARP (CircRNA identification using A-tailing RNase R approach and Pseudo-reference alignment), a comprehensive 21-module computational framework for accurate circRNA identification and quantification. Using CARP, we identify developmentally programmed human oligodendroglia circRNA landscapes in the HOG oligodendroglioma cell line, distinct from neuronal circRNA landscapes. Numerous circRNAs display oligodendroglia-specific regulation upon differentiation, among which a subclass is regulated independently from their parental mRNAs. We find that circRNA flanking introns often contain cis-regulatory elements for RNA editing and are predicted to bind differentiation-regulated splicing factors. In addition, we discover novel oligodendroglia-specific circRNAs that are predicted to sponge microRNAs, which co-operatively promote oligodendroglia development. Furthermore, we identify circRNA clusters derived from differentiation-regulated alternative circularization events within the same gene, each containing a common circular exon, achieving additive sponging effects that promote human oligodendroglia differentiation. Conclusions: Our results reveal dynamic regulation of human oligodendroglia circRNA landscapes during early differentiation and suggest critical roles of the circRNA-miRNA-mRNA axis in advancing human oligodendroglia development.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationLi Y, Wang F, Teng P, et al. Accurate identification of circRNA landscape and complexity reveals their pivotal roles in human oligodendroglia differentiation. Genome Biol. 2022;23(1):48. Published 2022 Feb 7. doi:10.1186/s13059-022-02621-1en_US
dc.identifier.urihttps://hdl.handle.net/1805/32793
dc.language.isoen_USen_US
dc.publisherBMCen_US
dc.relation.isversionof10.1186/s13059-022-02621-1en_US
dc.relation.journalGenome Biologyen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.sourcePMCen_US
dc.subjectCircRNAsen_US
dc.subjectMicroRNAsen_US
dc.subjectOL Differentiationen_US
dc.subjectOligodendrogliaen_US
dc.titleAccurate identification of circRNA landscape and complexity reveals their pivotal roles in human oligodendroglia differentiationen_US
dc.typeArticleen_US
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