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Accurate identification of circRNA landscape and complexity reveals their pivotal roles in human oligodendroglia differentiation
BACKGROUND: 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,...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819885/ https://www.ncbi.nlm.nih.gov/pubmed/35130952 http://dx.doi.org/10.1186/s13059-022-02621-1 |
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author | Li, Yangping Wang, Feng Teng, Peng Ku, Li Chen, Li Feng, Yue Yao, Bing |
author_facet | Li, Yangping Wang, Feng Teng, Peng Ku, Li Chen, Li Feng, Yue Yao, Bing |
author_sort | Li, Yangping |
collection | PubMed |
description | BACKGROUND: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-022-02621-1. |
format | Online Article Text |
id | pubmed-8819885 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-88198852022-02-08 Accurate identification of circRNA landscape and complexity reveals their pivotal roles in human oligodendroglia differentiation Li, Yangping Wang, Feng Teng, Peng Ku, Li Chen, Li Feng, Yue Yao, Bing Genome Biol Research BACKGROUND: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-022-02621-1. BioMed Central 2022-02-07 /pmc/articles/PMC8819885/ /pubmed/35130952 http://dx.doi.org/10.1186/s13059-022-02621-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Li, Yangping Wang, Feng Teng, Peng Ku, Li Chen, Li Feng, Yue Yao, Bing Accurate identification of circRNA landscape and complexity reveals their pivotal roles in human oligodendroglia differentiation |
title | Accurate identification of circRNA landscape and complexity reveals their pivotal roles in human oligodendroglia differentiation |
title_full | Accurate identification of circRNA landscape and complexity reveals their pivotal roles in human oligodendroglia differentiation |
title_fullStr | Accurate identification of circRNA landscape and complexity reveals their pivotal roles in human oligodendroglia differentiation |
title_full_unstemmed | Accurate identification of circRNA landscape and complexity reveals their pivotal roles in human oligodendroglia differentiation |
title_short | Accurate identification of circRNA landscape and complexity reveals their pivotal roles in human oligodendroglia differentiation |
title_sort | accurate identification of circrna landscape and complexity reveals their pivotal roles in human oligodendroglia differentiation |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819885/ https://www.ncbi.nlm.nih.gov/pubmed/35130952 http://dx.doi.org/10.1186/s13059-022-02621-1 |
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