miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA

被引：846

作者：

Hansen, Thomas B. ^{[1
]}

Wiklund, Erik D. ^{[1
,2
]}

Bramsen, Jesper B. ^{[1
]}

Villadsen, Sune B. ^{[1
]}

Statham, Aaron L. ^{[2
]}

Clark, Susan J. ^{[2
]}

Kjems, Jorgen ^{[1
]}

机构：

[1] Aarhus Univ, Dept Mol Biol, Interdisciplinary Nanosci Ctr iNANO, DK-8000 Aarhus C, Denmark

[2] St Vincents Hosp, Garvan Inst Med Res, Canc Program, Epigenet Lab, Darlinghurst, NSW 2010, Australia

来源：

EMBO JOURNAL | 2011年 / 30卷 / 21期

基金：

英国医学研究理事会;

关键词：

CDR1; circular RNA; miR-671; natural antisense transcript; nuclear microRNA; NEOPLASTIC CEREBELLAR DEGENERATION; HUMAN-CELLS; MESSENGER-RNAS; INTERFERING RNAS; MAMMALIAN-CELLS; DNA METHYLATION; LET-7; MICRORNA; NONCODING RNA; CANCER-CELLS; EXPRESSION;

D O I：

10.1038/emboj.2011.359

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

MicroRNAs (miRNAs) are similar to 22 nt non-coding RNAs that typically bind to the 3' UTR of target mRNAs in the cytoplasm, resulting in mRNA destabilization and translational repression. Here, we report that miRNAs can also regulate gene expression by targeting non-coding antisense transcripts in human cells. Specifically, we show that miR-671 directs cleavage of a circular antisense transcript of the Cerebellar Degeneration-Related protein 1 (CDR1) locus in an Ago2-slicer-dependent manner. The resulting downregulation of circular antisense has a concomitant decrease in CDR1 mRNA levels, independently of heterochromatin formation. This study provides the first evidence for non-coding antisense transcripts as functional miRNA targets, and a novel regulatory mechanism involving a positive correlation between mRNA and antisense circular RNA levels. The EMBO Journal (2011) 30, 4414-4422. doi:10.1038/emboj.2011.359; Published online 30 September 2011

引用

页码：4414 / 4422

页数：9

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