Publication Date:
2013-03-01
Description:
MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. Although the circRNA is completely resistant to miRNA-mediated target destabilization, it strongly suppresses miR-7 activity, resulting in increased levels of miR-7 targets. In the mouse brain, we observe overlapping co-expression of ciRS-7 and miR-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hansen, Thomas B -- Jensen, Trine I -- Clausen, Bettina H -- Bramsen, Jesper B -- Finsen, Bente -- Damgaard, Christian K -- Kjems, Jorgen -- England -- Nature. 2013 Mar 21;495(7441):384-8. doi: 10.1038/nature11993. Epub 2013 Feb 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and Genetics, Aarhus University, C.F. Mollers Alle 3, 8000C, Aarhus, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23446346" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Argonaute Proteins/metabolism
;
Brain/metabolism
;
*Gene Expression Regulation
;
HEK293 Cells
;
HeLa Cells
;
Humans
;
Male
;
Mice
;
Mice, Inbred C57BL
;
MicroRNAs/genetics/*metabolism
;
RNA/genetics/*metabolism
;
Sex-Determining Region Y Protein/genetics/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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