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
Fund:;Yak and beef cattle industry technology system of China;National Project of Scientific Innovation Experiment for undergraduate of Northwest A&F University;Technology Foundation for Selected Overseas Chinese Scholar of Shaanxi Province
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