The emerging roles of circular RNAs in regulating the fate of stem cells
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The emerging roles of circular RNAs in regulating the fate of stem cells Ziyao Zhuang1 · Lingfei Jia2,3 · Weiran Li1 · Yunfei Zheng1 Received: 18 May 2020 / Accepted: 2 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Circular RNAs(circRNAs) are a large family of RNAs shaping covalently closed ring-like molecules and have become a hotspot with thousands of newly published studies. Stem cells are undifferentiated cells and have great potential in medical treatment due to their self-renewal ability and differentiation capacity. Abundant researches have unveiled that circRNAs have unique expression profile during the differentiation of stem cells and could serve as promising biomarkers of these cells. There are key circRNAs relevant to the differentiation, proliferation, and apoptosis of stem cells with certain mechanisms such as sponging miRNAs, interacting with proteins, and interfering mRNA translation. Moreover, several circRNAs have joined in the interplay between stem cells and lymphocytes. Our review will shed lights on the emerging roles of circRNAs in regulating the fate of diverse stem cells. Keywords Circular RNA · Stem cells · Cell differentiation · Cell proliferation · Apoptosis
Introduction Circular RNAs(circRNAs) are a large class of non-coding RNAs forming covalently closed loop structures with neither 5′–3′ polarities nor polyadenylated tails, which are different from linear RNAs. CircRNAs are more stable than linear RNAs as a result of their ring structures protecting them from exonuclease-mediated degradation [1]. Unlike canonical linear splicing, circRNAs are produced from precursor mRNAs (pre-mRNAs) by a non-canonical splicing event called backsplicing in which a downstream splice-donor site is covalently linked to an upstream splice-acceptor site, thus forming a ring structure. The first report of circRNAs was published in 1976 by Sanger et al., who found viroids to be covalently closed circular RNA molecules [2]. However, circRNAs were regarded as experimental artifacts or * Yunfei Zheng [email protected] 1
Department of Orthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, People’s Republic of China
2
Central Laboratory, Peking University School and Hospital of Stomatology, Beijing 100081, People’s Republic of China
3
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, People’s Republic of China
accidental splicing by-products at that time [3]. Development of RNA deep sequencing and ribosomal RNA depletion technology made it possible to take a deeper look at circRNAs and a surprising work declared circRNAs to be extensive in human genes [4]. In 2013, two articles were posted simultaneously in Nature which discovered two circRNAs to be microRNA(miRNA) sponges: antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as) and circular sex-determining region Y (circSry), u
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