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

被引：6564

作者：

Memczak, Sebastian ^{[1
]}

Jens, Marvin ^{[1
]}

Elefsinioti, Antigoni ^{[1
]}

Torti, Francesca ^{[1
]}

Krueger, Janna ^{[1
]}

Rybak, Agnieszka ^{[1
]}

Maier, Luisa ^{[1
]}

Mackowiak, Sebastian D. ^{[1
]}

Gregersen, Lea H. ^{[1
]}

Munschauer, Mathias ^{[1
]}

Loewer, Alexander ^{[1
]}

Ziebold, Ulrike ^{[1
]}

Landthaler, Markus ^{[1
]}

Kocks, Christine ^{[1
]}

le Noble, Ferdinand ^{[1
]}

Rajewsky, Nikolaus ^{[1
]}

机构：

[1] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany

来源：

NATURE | 2013年 / 495卷 / 7441期

关键词：

BINDING PROTEIN; MESSENGER-RNA; NONCODING RNA; GENE; TRANSCRIPTS; EXPRESSION; MICRORNAS; SEQUENCE; DIFFERENTIATION; DISCOVERY;

D O I：

10.1038/nature11928

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：333 / 338

页数：6

共 51 条

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