Circular RNAs are a large class of animal RNAs with regulatory potency
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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.
In: Nature, Vol. 495, No. 7441, 21.03.2013, p. 333-8.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Circular RNAs are a large class of animal RNAs with regulatory potency
AU - Memczak, Sebastian
AU - Jens, Marvin
AU - Elefsinioti, Antigoni
AU - Torti, Francesca
AU - Krueger, Janna
AU - Rybak, Agnieszka
AU - Maier, Luisa
AU - Mackowiak, Sebastian D
AU - Gregersen, Lea H
AU - Munschauer, Mathias
AU - Loewer, Alexander
AU - Ziebold, Ulrike
AU - Landthaler, Markus
AU - Kocks, Christine
AU - le Noble, Ferdinand
AU - Rajewsky, Nikolaus
PY - 2013/3/21
Y1 - 2013/3/21
N2 - 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.
AB - 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.
KW - Animals
KW - Autoantigens/genetics
KW - Binding Sites
KW - Brain/metabolism
KW - Caenorhabditis elegans/genetics
KW - Cell Line
KW - Conserved Sequence
KW - Female
KW - Gene Expression Regulation
KW - HEK293 Cells
KW - Humans
KW - Male
KW - Mice
KW - MicroRNAs/genetics
KW - Nerve Tissue Proteins/genetics
KW - RNA/genetics
KW - RNA, Circular
KW - Zebrafish/embryology
U2 - 10.1038/nature11928
DO - 10.1038/nature11928
M3 - Journal article
C2 - 23446348
VL - 495
SP - 333
EP - 338
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7441
ER -
ID: 328236755