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PMID: 21964070 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 30 ·No. 21 ·2011-09-30 ·Pages 4414-22

Hansen TB, Wiklund ED, Bramsen JB, Villadsen SB, Statham AL, Clark SJ, Kjems J

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.

MeSH Terms
Argonaute Proteins/metabolism,physiology Autoantigens/genetics,metabolism Base Sequence Gene Expression Regulation/drug effects,genetics HEK293 Cells Humans MicroRNAs/pharmacology,physiology Models, Biological Molecular Sequence Data Nerve Tissue Proteins/genetics,metabolism Nucleic Acid Conformation RNA/drug effects,metabolism RNA Cleavage/drug effects,genetics,physiology RNA Interference/drug effects RNA Splicing/genetics,physiology RNA, Antisense/chemistry,metabolism RNA, Circular
Chemicals
AGO2 protein, human Argonaute Proteins Autoantigens CDR1 protein, human MIRN671 microRNA, human MicroRNAs Nerve Tissue Proteins RNA, Antisense RNA, Circular RNA
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Hansen Thomas B
Department of Molecular Biology, Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, Denmark.
Wiklund Erik D
Bramsen Jesper B
Villadsen Sune B
Statham Aaron L
Clark Susan J
Kjems Jørgen
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
1460-2075
DOI
10.1038/emboj.2011.359
Published
2011-09-30
Epub
2011-00-30
Pages
4414-22
Language
English
Region
England
NLM ID
8208664
PMCID
PMC3230379
Subset
IM
Corrections
CommentIn
PMID: 22048334
External Links
PubMed source DOI: 10.1038/emboj.2011.359 PMC Full Text View journal details
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