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      Mechanisms of circular RNA degradation

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          Abstract

          Circular RNAs (CircRNAs) are a class of noncoding RNAs formed by backsplicing during cotranscriptional and posttranscriptional processes, and they widely exist in various organisms. CircRNAs have multiple biological functions and are associated with the occurrence and development of many diseases. While the biogenesis and biological function of circRNAs have been extensively studied, there are few studies on circRNA degradation and only a few pathways for specific circRNA degradation have been identified. Here we outline basic information about circRNAs, summarize the research on the circRNA degradation mechanisms and discusses where this field might head, hoping to provide some inspiration and guidance for scholars who aim to study the degradation of circRNAs.

          Abstract

          In this Perspective, Longxin Ren and co-authors summarise the role of circular RNAs in disease and discuss recent insights into how circular RNAs are metabolised in the cell.

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          The biogenesis, biology and characterization of circular RNAs

          Lasse S. Kristensen, Maria Andersen, Lotte V. W. Stagsted … (2019)
          Circular RNAs (circRNAs) are covalently closed, endogenous biomolecules in eukaryotes with tissue-specific and cell-specific expression patterns, whose biogenesis is regulated by specific cis-acting elements and trans-acting factors. Some circRNAs are abundant and evolutionarily conserved, and many circRNAs exert important biological functions by acting as microRNA or protein inhibitors ('sponges'), by regulating protein function or by being translated themselves. Furthermore, circRNAs have been implicated in diseases such as diabetes mellitus, neurological disorders, cardiovascular diseases and cancer. Although the circular nature of these transcripts makes their detection, quantification and functional characterization challenging, recent advances in high-throughput RNA sequencing and circRNA-specific computational tools have driven the development of state-of-the-art approaches for their identification, and novel approaches to functional characterization are emerging.
          Article 0 comments Cited 1693 times – based on 0 reviews     Review now
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            Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis.

            Yan-Yan Li, Qiupeng Zheng, Chunyang Bao … (2015)
            Article 0 comments Cited 712 times – based on 0 reviews     Review now
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              The RNA binding protein quaking regulates formation of circRNAs.

              Simon Conn, Katherine A. Pillman, John Toubia … (2015)
              Circular RNAs (circRNAs), formed by non-sequential back-splicing of pre-mRNA transcripts, are a widespread form of non-coding RNA in animal cells. However, it is unclear whether the majority of circRNAs represent splicing by-products without function or are produced in a regulated manner to carry out specific cellular functions. We show that hundreds of circRNAs are regulated during human epithelial-mesenchymal transition (EMT) and find that the production of over one-third of abundant circRNAs is dynamically regulated by the alternative splicing factor, Quaking (QKI), which itself is regulated during EMT. Furthermore, by modulating QKI levels, we show the effect on circRNA abundance is dependent on intronic QKI binding motifs. Critically, the addition of QKI motifs is sufficient to induce de novo circRNA formation from transcripts that are normally linearly spliced. These findings demonstrate circRNAs are both purposefully synthesized and regulated by cell-type specific mechanisms, suggesting they play specific biological roles in EMT.
              Article 0 comments Cited 617 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Nanyang Yang:
                ORCID: http://orcid.org/0000-0001-9883-8386
                yangny204@usc.edu.cn
                Guoqing Li:
                ORCID: http://orcid.org/0000-0001-8169-0434
                guoqingli@usc.edu.cn
                Journal
                Journal ID (nlm-ta): Commun Biol
                Journal ID (iso-abbrev): Commun Biol
                Title: Communications Biology
                Publisher: Nature Publishing Group UK (London )
                ISSN (Electronic): 2399-3642
                Publication date (Electronic): 9 December 2022
                Publication date PMC-release: 9 December 2022
                Publication date Collection: 2022
                Volume: 5
                Electronic Location Identifier: 1355
                Affiliations
                [1 ]GRID grid.412017.1, ISNI 0000 0001 0266 8918, The Hengyang Key Laboratory of Cellular Stress Biology, Institute of Cytology and Genetics, Hengyang Medical School, , University of South China, ; Hengyang, 421001 Hunan China
                [2 ]GRID grid.412017.1, ISNI 0000 0001 0266 8918, Department of Otolaryngology, The First Affiliated Hospital, Hengyang Medical School, , University of South China, ; Hengyang, Hunan 421001 China
                [3 ]GRID grid.412017.1, ISNI 0000 0001 0266 8918, Department of Ultrasonography, Second Affiliated Hospital, , University of South China, ; Hengyang Hunan, 421001 China
                Author information
                http://orcid.org/0000-0001-9883-8386
                http://orcid.org/0000-0001-8169-0434
                Article
                Publisher ID: 4262
                DOI: 10.1038/s42003-022-04262-3
                PMC ID: 9734648
                PubMed ID: 36494488
                SO-VID: 497b189b-3530-4efc-b01f-64ded5b1fdb9
                Copyright © © The Author(s) 2022
                License:

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 10 May 2022
                Date accepted : 15 November 2022
                Funding
                Funded by: FundRef https://doi.org/10.13039/100009377, Education Department of Hunan Province (Hunan Province Education Department);
                Award ID: No. 19B500
                Award ID: No.21A0268
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100004735, Natural Science Foundation of Hunan Province (Hunan Provincial Natural Science Foundation);
                Award ID: No.2021JJ40480
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100010083, Hunan Provincial Innovation Foundation for Postgraduate;
                Award ID: No. CX20221006
                Award Recipient :
                Funded by: Project of Health Commission of Hunan Province (No. 202207014759), University Students Study and Innovation Pilot Project (No. 2022[174]-3222)
                Categories
                Subject: Perspective
                Custom metadata
                issue-copyright-statement © The Author(s) 2022

                Keywords: rna splicing,non-coding rnas,rna,rna decay
                Data availability:
                Keywords: rna splicing, non-coding rnas, rna, rna decay

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