The circular RNA circBIRC6 participates in the molecular circuitry controlling human pluripotency
Open accessAbstract
Accumulating evidence indicates that circular RNAs (circRNAs) are abundant in the human transcriptome. However, their involvement in biological processes, including pluripotency, remains mostly undescribed. We identified a subset of circRNAs that are enriched in undifferentiated human embryonic stem cells (hESCs) and demonstrated that two, circBIRC6 and circCORO1C, are functionally associated with the pluripotent state. Mechanistically, we found that circBIRC6 is enriched in the AGO2 complex and directly interacts with microRNAs, miR-34a, and miR-145, which are known to modulate target genes that maintain pluripotency. Correspondingly, circBIRC6 attenuates the downregulation of these target genes and suppresses hESC differentiation. We further identified hESC-enriched splicing factors (SFs) and demonstrated that circBIRC6 biogenesis in hESCs is promoted by the SF ESRP1, whose expression is controlled by the core pluripotency-associated factors, OCT4 and NANOG. Collectively, our data suggest that circRNA serves as a microRNA "sponge" to regulate the molecular circuitry, which modulates human pluripotency and differentiation.
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Modulation of MRE load with competing endogenous RNAs such as circular RNAs can sequester miRISC from target mRNA, leading to derepression of target mRNA.
“In this way, modulation of MRE load with competing endogenous RNAs (ceRNAs), such as with circular RNAs (circRNAs) (96), can act to sequester miRISC from target mRNA, leading to derepression of target mRNA (97).”
From Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation (2018) · cites this paper as [97]
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- Authors
- Yu, C.-Y., Li, T.-C., Wu, Y.-Y., Yeh, C.-H., Chiang, W., Chuang, C.-Y., & Kuo, H.-C.
- Affiliations
- Institute of Cellular and Organismic Biology, Academia Sinica (TW)
- Genomics Research Center, Academia Sinica (TW)
- National Taiwan University (TW)
- Corresponding author
- Kuo, Hung-Chih
- Venue
- Nature Communications
- Published
- 2017-10-27
- Volume
- 8
- Issue
- 1
- Pages
- 1149-1149
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5658440
- OpenAlex
- W2766512489
- Cited by
- 336
- References
- 43
- Citations by year
- 2026: 10 · 2025: 20 · 2024: 26 · 2023: 23 · 2022: 63 · 2021: 72 · 2020: 50 · 2019: 43 · 2018: 26 · 2017: 2
- FWCI
- 13.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Academia Sinica (AS-104-TP-B09, 105-0210-01-13-01, AS‐103‐TP‐B10)
- Ministry of Science and Technology, Taiwan (MOST103-2321-B001-065)
- National Health Research Institutes (NHRI-EX104-10320SI, EX104)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- circular RNA, human embryonic stem cells, miR-34a, miR-145, microRNA sponge, ESRP1, splicing factors, Oct4, Nanog, cell differentiation, circRNA biogenesis
- MeSH terms
- Nanog Homeobox Protein, RNA, Circular, Animals, Cell Differentiation, Exoribonucleases, Humans, Mice, Inbred ICR, Microfilament Proteins, RNA, Gene Expression Profiling, MicroRNAs, Pluripotent Stem Cells, Octamer Transcription Factor-3, Inhibitor of Apoptosis Proteins, Mice, Embryonic Stem Cells, Argonaute Proteins
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