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      • Record: found
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      Circular RNAs in Diabetic Nephropathy: Updates and Perspectives

      research-article
      Author(s): , * ,
      Publication date (Electronic):
      Journal: Aging and Disease
      Publisher: JKL International LLC
      Keywords: circular RNA, diabetic nephropathy, miRNA sponge, fibrosis

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          Abstract

          Circular RNAs (circRNAs) are widespread endogenous transcripts lacking 5′-caps and 3′-polyadenylation tails. Their closed-loop structure confers exonuclease resistance and extreme stability. CircRNAs play essential roles in various diseases, including diabetes. Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease and is one of the most common complications of diabetes. CircRNAs are key in DN and therefore important for understanding DN pathophysiology and developing new therapeutic strategies. In the present review, we briefly introduce the characteristics and functions of circRNAs and summarize recent discoveries on how circRNAs participate in DN. Based on these advances, we suggest future perspectives for studying circRNAs in DN to improve DN treatment and management.

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          Natural RNA circles function as efficient microRNA sponges.

          Thomas B. Hansen, Trine I. Jensen, Bettina H. Clausen … (2014)
          MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. Although the circRNA is completely resistant to miRNA-mediated target destabilization, it strongly suppresses miR-7 activity, resulting in increased levels of miR-7 targets. In the mouse brain, we observe overlapping co-expression of ciRS-7 and miR-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA.
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            Circular RNAs are abundant, conserved, and associated with ALU repeats.

            W. R. Jeck, J A Sorrentino, K. Wang … (2013)
            Circular RNAs composed of exonic sequence have been described in a small number of genes. Thought to result from splicing errors, circular RNA species possess no known function. To delineate the universe of endogenous circular RNAs, we performed high-throughput sequencing (RNA-seq) of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease, RNase R. We identified >25,000 distinct RNA species in human fibroblasts that contained non-colinear exons (a "backsplice") and were reproducibly enriched by exonuclease degradation of linear RNA. These RNAs were validated as circular RNA (ecircRNA), rather than linear RNA, and were more stable than associated linear mRNAs in vivo. In some cases, the abundance of circular molecules exceeded that of associated linear mRNA by >10-fold. By conservative estimate, we identified ecircRNAs from 14.4% of actively transcribed genes in human fibroblasts. Application of this method to murine testis RNA identified 69 ecircRNAs in precisely orthologous locations to human circular RNAs. Of note, paralogous kinases HIPK2 and HIPK3 produce abundant ecircRNA from their second exon in both humans and mice. Though HIPK3 circular RNAs contain an AUG translation start, it and other ecircRNAs were not bound to ribosomes. Circular RNAs could be degraded by siRNAs and, therefore, may act as competing endogenous RNAs. Bioinformatic analysis revealed shared features of circularized exons, including long bordering introns that contained complementary ALU repeats. These data show that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression.
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              circRNA biogenesis competes with pre-mRNA splicing.

              Reut Ashwal-Fluss, Markus Meyer, Nagarjuna Reddy Pamudurti … (2014)
              Circular RNAs (circRNAs) are widely expressed noncoding RNAs. However, their biogenesis and possible functions are poorly understood. Here, by studying circRNAs that we identified in neuronal tissues, we provide evidence that animal circRNAs are generated cotranscriptionally and that their production rate is mainly determined by intronic sequences. We demonstrate that circularization and splicing compete against each other. These mechanisms are tissue specific and conserved in animals. Interestingly, we observed that the second exon of the splicing factor muscleblind (MBL/MBNL1) is circularized in flies and humans. This circRNA (circMbl) and its flanking introns contain conserved muscleblind binding sites, which are strongly and specifically bound by MBL. Modulation of MBL levels strongly affects circMbl biosynthesis, and this effect is dependent on the MBL binding sites. Together, our data suggest that circRNAs can function in gene regulation by competing with linear splicing. Furthermore, we identified muscleblind as a factor involved in circRNA biogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Aging Dis
                Journal ID (iso-abbrev): Aging Dis
                Title: Aging and Disease
                Publisher: JKL International LLC
                ISSN (Electronic): 2152-5250
                Publication date Collection: 1 October 2022
                Publication date (Electronic): 1 October 2022
                Volume: 13
                Issue: 5
                Pages: 1365-1380
                Affiliations
                [1-ad-13-5-1365]Department of Nephrology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, China.
                Author notes
                [* ]Correspondence should be addressed to: Dr. Junli Zhao, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China. E-mail: zhaojunli1203@ 123456126.com.
                Article
                Publisher ID: ad-13-5-1365
                DOI: 10.14336/AD.2022.0203
                PMC ID: 9466972
                PubMed ID: 36186139
                SO-VID: b21f208b-b9d8-4dd0-b2d9-37add26388e4
                Copyright © copyright: © 2022 Liu et al.
                License:

                this is an open access article distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                Date received : 18 December 2021
                Date revision requested : 1 February 2022
                Date accepted : 2 February 2022
                Categories
                Subject: Perspective

                Keywords: circular rna,diabetic nephropathy,mirna sponge,fibrosis
                Data availability:
                Keywords: circular rna, diabetic nephropathy, mirna sponge, fibrosis

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