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      CircRNA Is a Rising Star in Researches of Ocular Diseases

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          Abstract

          A newly rediscovered subclass of noncoding RNAs, circular RNAs (circRNAs), is produced by a back-splicing mechanism with a covalently closed loop structure. They not only serve as the sponge for microRNAs (miRNAs) and proteins but also regulate gene expression and epigenetic modification, translate into peptides, and generate pseudogenes. Dysregulation of circRNA expression has opened a new chapter in the etiology of various human disorders, including cancer and cardiovascular, neurodegenerative, and ocular diseases. Recent studies recognized the vital roles that circRNAs played in the pathogenesis of various eye diseases, highlighting circRNAs as promising biomarkers for diagnosis and assessment of progression and prognosis. Interventions targeting circRNAs provide insights for developing novel treatments for these ocular diseases. This review summarizes our current perception of the properties, biogenesis, and functions of circRNAs and the development of circRNA researches related to ophthalmologic diseases, including diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, glaucoma, corneal neovascularization, cataract, pterygium, proliferative vitreoretinopathy, retinoblastoma, and ocular melanoma.

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          Most cited references74

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          Genome-wide analysis of drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation.

          Circularization was recently recognized to broadly expand transcriptome complexity. Here, we exploit massive Drosophila total RNA-sequencing data, >5 billion paired-end reads from >100 libraries covering diverse developmental stages, tissues, and cultured cells, to rigorously annotate >2,500 fruit fly circular RNAs. These mostly derive from back-splicing of protein-coding genes and lack poly(A) tails, and the circularization of hundreds of genes is conserved across multiple Drosophila species. We elucidate structural and sequence properties of Drosophila circular RNAs, which exhibit commonalities and distinctions from mammalian circles. Notably, Drosophila circular RNAs harbor >1,000 well-conserved canonical miRNA seed matches, especially within coding regions, and coding conserved miRNA sites reside preferentially within circularized exons. Finally, we analyze the developmental and tissue specificity of circular RNAs and note their preferred derivation from neural genes and enhanced accumulation in neural tissues. Interestingly, circular isoforms increase substantially relative to linear isoforms during CNS aging and constitute an aging biomarker. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
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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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              Coordinated circRNA Biogenesis and Function with NF90/NF110 in Viral Infection

              Circular RNAs (circRNAs) generated via back-splicing are enhanced by flanking complementary sequences. Expression levels of circRNAs vary under different conditions, suggesting participation of protein factors in their biogenesis. Using genome-wide siRNA screening that targets all human unique genes and an efficient circRNA expression reporter, we identify double-stranded RNA-binding domain containing immune factors NF90/NF110 as key regulators in circRNA biogenesis. NF90/NF110 promote circRNA production in the nucleus by associating with intronic RNA pairs juxtaposing the circRNA-forming exon(s); they also interact with mature circRNAs in the cytoplasm. Upon viral infection, circRNA expression is decreased, in part owing to the nuclear export of NF90/NF110 to the cytoplasm. Meanwhile, NF90/NF110 released from circRNP complexes bind to viral mRNAs as part of their functions in antiviral immune response. Our results therefore implicate a coordinated regulation of circRNA biogenesis and function by NF90/NF110 in viral infection.
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                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                03 September 2020
                2020
                : 8
                : 850
                Affiliations
                [1] 1Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou, China
                [2] 2Department of Ophthalmology, Jiande Branch, The Second Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou, China
                Author notes

                Edited by: Rachida Bouhenni, Akron Children’s Hospital, United States

                Reviewed by: Ye Sun, Boston Children’s Hospital and Harvard Medical School, United States; Ross F. Collery, Medical College of Wisconsin, United States

                *Correspondence: Yibo Yu, yuyibo@ 123456zju.edu.cn

                This article was submitted to Molecular Medicine, a section of the journal Frontiers in Cell and Developmental Biology

                Article
                10.3389/fcell.2020.00850
                7494781
                33015046
                46ff80c2-c8f1-499d-aeb8-4609a0d11af1
                Copyright © 2020 Zhang, Hu and Yu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 19 June 2020
                : 07 August 2020
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 139, Pages: 15, Words: 0
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81470612
                Award ID: 81670832
                Funded by: Natural Science Foundation of Zhejiang Province 10.13039/501100004731
                Award ID: LY20H120011
                Categories
                Cell and Developmental Biology
                Review

                circular rna,noncoding rna,microrna sponge,ocular diseases,ophthalmology

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