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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. ; Gregersen, Lea H. ; Munschauer, Mathias ; Loewer, Alexander ; Ziebold, Ulrike ; Landthaler, Markus ; Kocks, Christine ; Le Noble, Ferdinand ; Rajewsky, Nikolaus (2013):
Circular RNAs are a large class of animal RNAs with regulatory potency.
In: Nature, 495 (7441), pp. 333-8. ISSN 1476-4687,
[Article]

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.

Item Type: Article
Erschienen: 2013
Creators: Memczak, Sebastian ; Jens, Marvin ; Elefsinioti, Antigoni ; Torti, Francesca ; Krueger, Janna ; Rybak, Agnieszka ; Maier, Luisa ; Mackowiak, Sebastian D. ; Gregersen, Lea H. ; Munschauer, Mathias ; Loewer, Alexander ; Ziebold, Ulrike ; Landthaler, Markus ; Kocks, Christine ; Le Noble, Ferdinand ; Rajewsky, Nikolaus
Title: Circular RNAs are a large class of animal RNAs with regulatory potency.
Language: English
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.

Journal or Publication Title: Nature
Journal Volume: 495
Issue Number: 7441
Divisions: 10 Department of Biology
10 Department of Biology > Systems Biology of the Stress Response
Date Deposited: 02 Sep 2015 08:33
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