Circular RNA: metabolism, functions and interactions with proteins
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REVIEW
Open Access
Circular RNA: metabolism, functions and interactions with proteins Wei-Yi Zhou1†, Ze-Rong Cai1†, Jia Liu1†, De-Shen Wang1, Huai-Qiang Ju1,2* and Rui-Hua Xu1,2*
Abstract Circular RNAs (CircRNAs) are single-stranded, covalently closed RNA molecules that are ubiquitous across species ranging from viruses to mammals. Important advances have been made in the biogenesis, regulation, localization, degradation and modification of circRNAs. CircRNAs exert biological functions by acting as transcriptional regulators, microRNA (miR) sponges and protein templates. Moreover, emerging evidence has revealed that a group of circRNAs can serve as protein decoys, scaffolds and recruiters. However, the existing research on circRNAprotein interactions is quite limited. Hence, in this review, we briefly summarize recent progress in the metabolism and functions of circRNAs and elaborately discuss the patterns of circRNA-protein interactions, including altering interactions between proteins, tethering or sequestering proteins, recruiting proteins to chromatin, forming circRNA-protein-mRNA ternary complexes and translocating or redistributing proteins. Many discoveries have revealed that circRNAs have unique expression signatures and play crucial roles in a variety of diseases, enabling them to potentially act as diagnostic biomarkers and therapeutic targets. This review systematically evaluates the roles and mechanisms of circRNAs, with the hope of advancing translational medicine involving circRNAs. Keywords: CircRNA, CircRNA-protein interaction, Mechanism, Metabolism, Function
Introduction Single-stranded, covalently closed circRNAs were first reported as viroids, which are pathogens of certain plants, in 1976 [1] and were first detected in human HeLa cells by electron microscopy in 1979 [2]. Later, more studies found or synthesized circular forms of RNAs in various species, including viruses [3], prokaryotes [4], unicellular eukaryotes [4, 5] and mammals [6]. With the development of high-throughput RNA-sequencing and bioinformatic tools, scientists have found that circRNA is a general feature of the human transcriptome and is ubiquitous in many other metazoans [7–9]. More recently, an increasing number of investigations have identified multiple functions of circRNAs, including * Correspondence: [email protected]; [email protected] † Wei-Yi Zhou, Ze-Rong Cai and Jia Liu contributed equally to this work. 1 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China Full list of author information is available at the end of the article
serving as protein scaffolds or miR sponges and being translated into polypeptides [7, 8, 10]. The unique structure of circRNAs provides them with a longer half-life and more resistance to RNase R than linear RNAs [11], which makes them potential candidates for diagnostic biomarkers and therapeutic targets. Plenty of studies have uncovered their distinct expression signatu
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