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

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  • Thomas Birkballe Hansen
  • Erik D Wiklund
  • ,
  • Jesper Bertram Bramsen
  • Sune B Villadsen
  • ,
  • Aaron L Statham, 2.Epigenetics Laboratory, Cancer Program, Garvan Institute of Medical Research, Australia
  • Susan J Clark, 2.Epigenetics Laboratory, Cancer Program, Garvan Institute of Medical Research, Australia
  • Jørgen Kjems
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 languageEnglish
JournalE M B O Journal
Volume30
Issue21
Pages (from-to)4414-4422
Number of pages9
ISSN0261-4189
DOIs
Publication statusPublished - 30 Sep 2011

    Research areas

  • CDR1, circular RNA, miR-671, natural antisense transcript, nuclear microRNA

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