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

Thomas Birkballe Hansen; Erik D Wiklund; Jesper Bertram Bramsen; Sune B Villadsen; Aaron L Statham; Susan J Clark; Jørgen Kjems

doi:10.1038/emboj.2011.359

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

Thomas Birkballe Hansen, Erik D Wiklund, Jesper Bertram Bramsen, Sune B Villadsen, Aaron L Statham, Susan J Clark, Jørgen Kjems

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

861 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) are ∼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.

Original language	English
Journal	E M B O Journal
Volume	30
Issue	21
Pages (from-to)	4414-4422
Number of pages	9
ISSN	0261-4189
DOIs	https://doi.org/10.1038/emboj.2011.359
Publication status	Published - 30 Sept 2011

Keywords

CDR1
circular RNA
miR-671
natural antisense transcript
nuclear microRNA

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10.1038/emboj.2011.359

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title = "miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA",

abstract = "MicroRNAs (miRNAs) are ∼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.",

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doi = "10.1038/emboj.2011.359",

language = "English",

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miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. / Hansen, Thomas Birkballe; Wiklund, Erik D; Bramsen, Jesper Bertram et al.
In: E M B O Journal, Vol. 30, No. 21, 30.09.2011, p. 4414-4422.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA

AU - Hansen, Thomas Birkballe

AU - Wiklund, Erik D

AU - Bramsen, Jesper Bertram

AU - Villadsen, Sune B

AU - Statham, Aaron L

AU - Clark, Susan J

AU - Kjems, Jørgen

PY - 2011/9/30

Y1 - 2011/9/30

N2 - MicroRNAs (miRNAs) are ∼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.

AB - MicroRNAs (miRNAs) are ∼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.

KW - CDR1

KW - circular RNA

KW - miR-671

KW - natural antisense transcript

KW - nuclear microRNA

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DO - 10.1038/emboj.2011.359

M3 - Journal article

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EP - 4422

JO - E M B O Journal

JF - E M B O Journal

IS - 21

ER -

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

Abstract

Keywords

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