环状RNA的分子特征、作用机制及生物学功能

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摘要环状RNA(circular RNA, circRNA)是一类经反向剪接后、由3'末端和5'末端共价结合形成的环状非编码RNA(non-coding RNA, ncRNA)分子，广泛存在于多种生物细胞中，具有结构稳定、序列保守及细胞或组织特异性表达等特征。目前研究表明，circRNA 可通过多种途径发挥作用。其可作为天然微小RNA(microRNA, miRNA)海绵参与其表达调控；也可通过与蛋白互作调节基因的转录、细胞周期或衰老等生理过程。此外，circRNA还与人类健康杀手如癌症和心脏病等多种疾病的调控过程密切相关，其在神经发育、免疫等过程中也扮演一定角色，具有重要的研究价值。本文主要对circRNA的形成机制与分子特征、作用机制、相关研究方法及其在疾病等生理病理过程中的研究现状进行了综述，同时讨论了circRNA研究中尚未解决的问题及其未来的应用前景。总而言之，circRNA的存在及功能拓展了真核生物转录组的复杂性和多样性，本文认为，对circRNA 的深入探究会丰富后基因组时代的研究内容，同时为更好的了解与治疗人类疾病提供理论依据与技术指导。

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	周凤燕
	杨青
	朱熙春
	蓝贤勇
	陈宏

关键词 ：环状RNA, 分子特征, 作用机制, 研究方法, 生物学功能

Abstract：Circular RNA (circRNA) is a group of non-coding RNA (ncRNA) characterized by the presence of a covalent bond linking 3' and 5' ends produced by backsplicing. It widely spreads and has the features of construct stability, sequence conservative, cell or tissue-specific expression and so on. So far, circRNA has been found exist in different species extensively and already three classes of circRNA have been detected, including exonic circRNA, circular intronic RNA (ciRNA) and exon-intron RNA (ElciRNA). Concerning the biogenesis of these circRNAs, scientists purposed six models in total, among them, three models clarified the formation of exonic circRNA and ElciRNA, and the others explained the generation of ciRNA. As research continues, there were lots of experiments support these models directly or indirectly. Moreover, some papers reported that the biogenesis of circRNA was regulated by splicing factors, such as SR, hnRNP and RBM20 etc. Relative researches showed that circRNA performs its function through various channels. Part of circRNAs act as natural microRNA (miRNA) spong to regulate the expression of them, and ciRNA or ElciRNA interacts with snRNP and recruits RNA Polymerase Ⅱ in the promoter region of the host-gene around where they are derived to regulate gene expression in cis. Besides, some circRNAs could regulate cell cycle or ageing etc. by interacting with protein. Although there was no evidence to show that circRNA can be translated in eukaryotes, some groups have found a number of virus circRNAs and viroid circRNAs could be translated into protein. Notably, circRNA is closely related to the diseases such as cancer (including breast cancer, lung cancer, hepatocellular carcinoma etc.) and cardiopathy, which are known as human healthy killer, it also plays a role in neurodevelopment, immune and other physiological process, indicating its significant value. This paper summarized the formation mechanism and features of circRNA, as well as the recent advance of circRNA in mainly function, relative research methods and the relationship with disease, at the last part of this paper, we discussed the unresolved issues about circRNA, such as which type of spliceosomes participate in back-splicing and how do them assembly and work? How the nucleocytoplasmic export of circRNA is regulated? as well as how circRNA is ultimately degraded. In general, circRNA extend the diversity and complexity of eukaryotic transcriptomes, and we believe that delve into circRNA will enrich the study content of the post-genome era and provide theoretical basis and technical guidance for better understanding, diagnosing and treatment of human diseases

Key words： Circular RNA Molecular feature Action Mechanism Research method Biology function

收稿日期: 2016-08-29 出版日期: 2017-03-02

ZTFLH:

基金资助:国家自然科学基金项目;国家肉牛牦牛产业技术体系;国家级大学生科创项目;陕西省留学人员科技活动择优资助项目

通讯作者: 蓝贤勇 E-mail: lan342@126.com

引用本文:

周凤燕杨青朱熙春蓝贤勇陈宏. 环状RNA的分子特征、作用机制及生物学功能[J]. , 2017, 25(3): 485-501.

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http://journal05.magtech.org.cn/Jwk_ny/CN/ 或 http://journal05.magtech.org.cn/Jwk_ny/CN/Y2017/V25/I3/485

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