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      Identifying and Characterizing circRNA-Protein Interaction

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          Abstract

          Circular RNAs have been identified as naturally occurring RNAs that are highly represented in the eukaryotic transcriptome. Although a large number of circRNAs have been reported, circRNA functions remain largely unknown. CircRNAs can function as miRNA sponges, thereby reducing their ability to target mRNAs. We hypothesize that circRNAs may bind, store, sort, and sequester proteins to particular subcellular locations, and act as dynamic scaffolding molecules that modulate protein-protein interactions. Here, we review the biological implication and function of circRNA-protein interaction, and reveal a dynamic model of the interaction in various tissues, development stages and physiological conditions. Improved techniques to identify and characterize the dynamic RNA-protein interactions may elucidate the molecular mechanisms associated with the expression and functional diversity of circRNAs.

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          Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses

          Circular RNAs are a subclass of non-coding RNAs detected within mammalian cells. This study was designed to test the roles of a circular RNA circ-Foxo3 in senescence using in vitro and in vivo approaches.
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            Circular RNAs: splicing's enigma variations.

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              Foxo3 activity promoted by non-coding effects of circular RNA and Foxo3 pseudogene in the inhibition of tumor growth and angiogenesis.

              It has recently been shown that the upregulation of a pseudogene specific to a protein-coding gene could function as a sponge to bind multiple potential targeting microRNAs (miRNAs), resulting in increased gene expression. Similarly, it was recently demonstrated that circular RNAs can function as sponges for miRNAs, and could upregulate expression of mRNAs containing an identical sequence. Furthermore, some mRNAs are now known to not only translate protein, but also function to sponge miRNA binding, facilitating gene expression. Collectively, these appear to be effective mechanisms to ensure gene expression and protein activity. Here we show that expression of a member of the forkhead family of transcription factors, Foxo3, is regulated by the Foxo3 pseudogene (Foxo3P), and Foxo3 circular RNA, both of which bind to eight miRNAs. We found that the ectopic expression of the Foxo3P, Foxo3 circular RNA and Foxo3 mRNA could all suppress tumor growth and cancer cell proliferation and survival. Our results showed that at least three mechanisms are used to ensure protein translation of Foxo3, which reflects an essential role of Foxo3 and its corresponding non-coding RNAs.
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                Author and article information

                Journal
                Theranostics
                Theranostics
                thno
                Theranostics
                Ivyspring International Publisher (Sydney )
                1838-7640
                2017
                26 September 2017
                : 7
                : 17
                : 4183-4191
                Affiliations
                [1 ]Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto;
                [2 ]Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto;
                [3 ]State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangzhou, 510070, China;
                [4 ]Yuewei Edible Fungi Technology Co. Ltd., Guangzhou, 510070, China;
                [5 ]Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), H-12 Islamabad, Pakistan;
                [6 ]Institute of Medical Science, University of Toronto, Toronto, Canada.
                Author notes
                ✉ Corresponding author: BB Yang, S110, S-Wing Research Building, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto M4N 3M5 Canada, tel: (416) 480-5874 e-mail: byang@ 123456sri.utoronto.ca

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                thnov07p4183
                10.7150/thno.21299
                5695005
                29158818
                1111e388-9efd-467b-9eb1-ecfe61cd1e3a
                © Ivyspring International Publisher

                This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 2 June 2017
                : 4 August 2017
                Categories
                Review

                Molecular medicine
                Molecular medicine

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