Abstract
Original language | English |
---|---|
Journal | Nature |
Volume | 495 |
Issue number | 7441 |
Pages (from-to) | 384-8 |
ISSN | 0028-0836 |
DOIs | |
Publication status | Published - 21. Mar 2013 |
Fingerprint
Keywords
- Animals
- Argonaute Proteins
- Brain
- Gene Expression Regulation
- HEK293 Cells
- HeLa Cells
- Humans
- Male
- Mice
- Mice, Inbred C57BL
- MicroRNAs
- RNA
- Sex-Determining Region Y Protein
Cite this
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Natural RNA circles function as efficient microRNA sponges. / Hansen, Thomas B; Jensen, Trine I; Clausen, Bettina H; Bramsen, Jesper Bertram; Finsen, Bente; Damgaard, Christian Kroun; Kjems, Jørgen.
In: Nature, Vol. 495, No. 7441, 21.03.2013, p. 384-8.Research output: Contribution to journal › Letter › Research › peer-review
TY - JOUR
T1 - Natural RNA circles function as efficient microRNA sponges
AU - Hansen, Thomas B
AU - Jensen, Trine I
AU - Clausen, Bettina H
AU - Bramsen, Jesper Bertram
AU - Finsen, Bente
AU - Damgaard, Christian Kroun
AU - Kjems, Jørgen
PY - 2013/3/21
Y1 - 2013/3/21
N2 - 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.
AB - 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.
KW - Animals
KW - Argonaute Proteins
KW - Brain
KW - Gene Expression Regulation
KW - HEK293 Cells
KW - HeLa Cells
KW - Humans
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - MicroRNAs
KW - RNA
KW - Sex-Determining Region Y Protein
U2 - 10.1038/nature11993
DO - 10.1038/nature11993
M3 - Letter
VL - 495
SP - 384
EP - 388
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7441
ER -