The circular RNA circBIRC6 participates in the molecular circuitry controlling human pluripotency
Chun-Ying Yu,
Tung-Cheng Li,
Yi-Ying Wu,
Chan-Hsien Yeh,
Wei Chiang,
Ching-Yu Chuang and
Hung-Chih Kuo ()
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Chun-Ying Yu: Academia Sinica
Tung-Cheng Li: Academia Sinica
Yi-Ying Wu: Academia Sinica
Chan-Hsien Yeh: Academia Sinica
Wei Chiang: Academia Sinica
Ching-Yu Chuang: Academia Sinica
Hung-Chih Kuo: Academia Sinica
Nature Communications, 2017, vol. 8, issue 1, 1-15
Abstract:
Abstract 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.
Date: 2017
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DOI: 10.1038/s41467-017-01216-w
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