title: 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.
authors: Systems Biology of Gene Regulatory Elements, Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors: Sebastian
authors: S
authors: Memczak
authors: Marvin
authors: M
authors: Jens
authors: Antigoni
authors: A
authors: Elefsinioti
authors: Francesca
authors: F
authors: Torti
authors: Janna
authors: J
authors: Krueger
authors: Agnieszka
authors: A
authors: Rybak
authors: Luisa
authors: L
authors: Maier
authors: Sebastian D
authors: SD
authors: Mackowiak
authors: Lea H
authors: LH
authors: Gregersen
authors: Mathias
authors: M
authors: Munschauer
authors: Alexander
authors: A
authors: Loewer
authors: Ulrike
authors: U
authors: Ziebold
authors: Markus
authors: M
authors: Landthaler
authors: Christine
authors: C
authors: Kocks
authors: Ferdinand
authors: F
authors: le Noble
authors: Nikolaus
authors: N
authors: Rajewsky
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D017124:Conserved Sequence; D005260:Female; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D000079962:RNA, Circular; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism
chemical_list: D001324:Autoantigens; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D012313:RNA; D000079962:RNA, Circular; C063762:CDR1 protein, human; C549242:MIRN7-1 microRNA, human