Cited by 7,990Circular RNAs in diseasesRNA Research and SplicingCancer-related molecular mechanisms research

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

Memczak, Sebastian, Jens, Marvin, Elefsinioti, Antigoni, Torti, Francesca, Krueger, Janna, Rybak, Agnieszka, Maier, Luisa, Mackowiak, Sebastian D. +8 more·2013·Nature

Abstract

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.

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Crossref · 10.1038/nature11928

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Authors
Memczak, S., Jens, M., Elefsinioti, A., Torti, F., Krueger, J., Rybak, A., Maier, L., Mackowiak, S. D., Gregersen, L. H., Munschauer, M., Loewer, A., Ziebold, U., Landthaler, M., Kocks, C., le Noble, F., & Rajewsky, N.
Affiliations
Max Delbrück Center (DE)
Corresponding author
Rajewsky, Nikolaus
Venue
Nature
Published
2013-02-27
Volume
495
Issue
7441
Pages
333-338
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2058835062
Cited by
7,990
References
79
Citations by year
2026: 320 · 2025: 436 · 2024: 677 · 2023: 741 · 2022: 1054 · 2021: 1193 · 2020: 1067 · 2019: 839 · 2018: 597 · 2017: 395 · 2016: 221 · 2015: 183 · 2014: 158 · 2013: 91 · 2012: 3
FWCI
97.57
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
circular RNA, CDR1as, miR-7, microRNA sponge, post-transcriptional regulation, microRNA binding sites, midbrain development, zebrafish, tissue-specific gene expression
MeSH terms
RNA, Circular, Animals, Autoantigens, Binding Sites, Brain, Cell Line, Female, Gene Expression Regulation, Humans, Male, Nerve Tissue Proteins, RNA, Zebrafish, Conserved Sequence, Caenorhabditis elegans, MicroRNAs, Mice, HEK293 Cells

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