2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      circAtlas 3.0: a gateway to 3 million curated vertebrate circular RNAs based on a standardized nomenclature scheme

      research-article
      , ,
      Nucleic Acids Research
      Oxford University Press

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Recent studies have demonstrated the important regulatory role of circRNAs, but an in-depth understanding of the comprehensive landscape of circRNAs across various species still remains unexplored. The current circRNA databases are often species-restricted or based on outdated datasets. To address this challenge, we have developed the circAtlas 3.0 database, which contains a rich collection of 2674 circRNA sequencing datasets, curated to delineate the landscape of circRNAs within 33 distinct tissues spanning 10 vertebrate species. Notably, circAtlas 3.0 represents a substantial advancement over its precursor, circAtlas 2.0, with the number of cataloged circRNAs escalating from 1 007 087 to 3 179 560, with 2 527 528 of them being reconstructed into full-length isoforms. circAtlas 3.0 also introduces several notable enhancements, including: (i) integration of both Illumina and Nanopore sequencing datasets to detect circRNAs of extended lengths; (ii) employment of a standardized nomenclature scheme for circRNAs, providing information of the host gene and full-length circular exons; (iii) inclusion of clinical cancer samples to explore the biological function of circRNAs within the context of cancer and (iv) links to other useful resources to enable user-friendly analysis of target circRNAs. The updated circAtlas 3.0 provides an important platform for exploring the evolution and biological implications of vertebrate circRNAs, and is freely available at http://circatlas.biols.ac.cn and https://ngdc.cncb.ac.cn/circatlas.

          Graphical Abstract

          Graphical Abstract

          Related collections

          Most cited references63

          • Record: found
          • Abstract: found
          • Article: not found

          Circular RNAs are a large class of animal RNAs with regulatory potency.

          Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Natural RNA circles function as efficient microRNA sponges.

            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.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Predicting effective microRNA target sites in mammalian mRNAs

              MicroRNA targets are often recognized through pairing between the miRNA seed region and complementary sites within target mRNAs, but not all of these canonical sites are equally effective, and both computational and in vivo UV-crosslinking approaches suggest that many mRNAs are targeted through non-canonical interactions. Here, we show that recently reported non-canonical sites do not mediate repression despite binding the miRNA, which indicates that the vast majority of functional sites are canonical. Accordingly, we developed an improved quantitative model of canonical targeting, using a compendium of experimental datasets that we pre-processed to minimize confounding biases. This model, which considers site type and another 14 features to predict the most effectively targeted mRNAs, performed significantly better than existing models and was as informative as the best high-throughput in vivo crosslinking approaches. It drives the latest version of TargetScan (v7.0; targetscan.org), thereby providing a valuable resource for placing miRNAs into gene-regulatory networks. DOI: http://dx.doi.org/10.7554/eLife.05005.001
                Bookmark

                Author and article information

                Contributors
                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                05 January 2024
                22 September 2023
                22 September 2023
                : 52
                : D1
                : D52-D60
                Affiliations
                Beijing Institutes of Life Science, Chinese Academy of Sciences , Beijing 100101, China
                Beijing Institutes of Life Science, Chinese Academy of Sciences , Beijing 100101, China
                University of Chinese Academy of Sciences , Beijing 100049, China
                Key Laboratory of Systems Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Chinese Academy of Sciences , Hangzhou, China
                Beijing Institutes of Life Science, Chinese Academy of Sciences , Beijing 100101, China
                Author notes
                To whom correspondence should be addressed. Tel: +86 10 84504372; Fax: +86 10 84504372; Email: zhangjinyang@ 123456biols.ac.cn
                Correspondence may also be addressed to Fangqing Zhao. Tel: +86 10 84504172; Fax: +86 10 84504172; Email: zhfq@ 123456biols.ac.cn
                Author information
                https://orcid.org/0000-0002-6202-1830
                https://orcid.org/0000-0002-6216-1235
                https://orcid.org/0000-0002-5163-894X
                Article
                gkad770
                10.1093/nar/gkad770
                10767913
                37739414
                df23e4e9-a8b9-45b7-a018-be4ca48a7614
                © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 08 September 2023
                : 31 August 2023
                : 12 August 2023
                Page count
                Pages: 9
                Funding
                Funded by: National Natural Science Foundation of China, DOI 10.13039/501100001809;
                Award ID: 32025009
                Award ID: 32130020
                Award ID: 32200530
                Funded by: National Key R&D Project;
                Award ID: 2021YFA1300500
                Award ID: 2021YFA1302000
                Funded by: China National Postdoctoral Program for Innovative Talents;
                Award ID: BX20220296
                Funded by: China Postdoctoral Science Foundation, DOI 10.13039/501100002858;
                Award ID: 2022M723134
                Funded by: Special Research Assistant of the Chinese Academy of Science;
                Categories
                AcademicSubjects/SCI00010
                Database Issue

                Genetics
                Genetics

                Comments

                Comment on this article