Circular RNAs are a large class of animal RNAs with regulatory potency
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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circRNAs function as a class of post-transcriptional regulators.
“These RNA molecules function as a class of post-transcriptional regulators.288”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [288]
The circRNA of human CDR1as/ciRS-7 is a miR-7 sponge, harbors 74 binding sites for miR-7, and binds to the argonaute (AGO) protein in a miR-7-dependent manner; this allows it to participate in the initiation and progression of PD.
“Interestingly, the circRNA of human CDR1as/ciRS-7 is a miR-7 sponge, which harbors 74 binding sites for miR-7 and is able to bind to the argonaute (AGO) protein in a miR-7-dependent manner.Binding to the AGO protein allows the circRNA of human CDR1as/ciRS-7 to participate in the initiation and progression of PD [14,70].”
From Circular RNAs in depression: Biogenesis, function, expression, and therapeutic potential (2021) · cites this paper as [70]
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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
- ORCID
- 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
- Licence
- www.springer.com/tdm (tdm)
- 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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