Xiao Juan, Joseph Shija, Xia Mengwei, Teng Feng, Chen Xuejiao, Huang Rufeng, Zhai Lihong, Deng Wenbin
School of Basic Medicine, Hubei University of Arts and Science, Xiangyang 441053, China.
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 510060, China.
J Clin Med. 2022 May 20;11(10):2909. doi: 10.3390/jcm11102909.
Circular RNAs (circRNAs), a novel type of endogenous RNAs, have become a subject of intensive research. It has been found that circRNAs are important players in cell differentiation and tissue homeostasis, as well as disease development. Moreover, the expression of circRNAs is usually not correlated with their parental gene expression, indicating that they are not only a steady-state by-product of mRNA splicing but a product of variable splicing under novel regulation. Sequence conservation analysis has also demonstrated that circRNAs have important non-coding functions. CircRNAs exist as a covalently closed loop form in mammalian cells, where they regulate cellular transcription and translation processes. CircRNAs are built from pre-messenger RNAs, and their biogenesis involves back-splicing, which is catalyzed by spliceosomes. The splicing reaction gives rise to three different types of intronic, exotic and exon-intron circular RNAs. Due to higher nuclease stability and longer half lives in cells, circRNAs are more stable than linear RNAs and have enormous clinical advantage for use as diagnostic and therapeutic biomarkers for disease. In recent years, it has been reported that circRNAs in stem cells play a crucial role in stem cell function. In this article, we reviewed the general feature of circRNAs and the distinct roles of circRNAs in stem cell biology, including regulation of stem cell self-renewal and differentiation. CircRNAs have shown unique expression profiles during differentiation of stem cells and could serve as promising biomarkers of these cells. As circRNAs play pivotal roles in stem cell regulation as well as the development and progression of various diseases, we also discuss opportunities and challenges of circRNA-based treatment strategies in future effective therapies for promising clinical applications.
环状RNA（circRNAs）是一类新型的内源性RNA，已成为深入研究的对象。研究发现，circRNAs在细胞分化、组织稳态以及疾病发展过程中发挥着重要作用。此外，circRNAs的表达通常与其亲本基因的表达无关，这表明它们不仅是mRNA剪接的稳态副产物，而且是在新调控下可变剪接的产物。序列保守性分析也表明，circRNAs具有重要的非编码功能。circRNAs以共价闭环形式存在于哺乳动物细胞中，在其中调节细胞转录和翻译过程。circRNAs由前体信使RNA形成，其生物合成涉及反向剪接，这一过程由剪接体催化。剪接反应产生三种不同类型的内含子、外显子和外显子-内含子环状RNA。由于在细胞中具有更高的核酸酶稳定性和更长的半衰期，circRNAs比线性RNA更稳定，在用作疾病的诊断和治疗生物标志物方面具有巨大的临床优势。近年来，有报道称干细胞中的circRNAs在干细胞功能中起关键作用。在本文中，我们综述了circRNAs的一般特征以及circRNAs在干细胞生物学中的独特作用，包括对干细胞自我更新和分化的调节。circRNAs在干细胞分化过程中表现出独特的表达谱，可作为这些细胞有前景的生物标志物。由于circRNAs在干细胞调控以及各种疾病的发生和发展中起关键作用，我们还讨论了基于circRNA的治疗策略在未来有前景的临床应用有效治疗中的机遇和挑战。
