Assessing the ceRNA Hypothesis with Quantitative Measurements of miRNA and Target Abundance

被引:544
作者
Denzler, Remy [1 ,2 ]
Agarwal, Vikram [3 ,4 ,5 ,6 ]
Stefano, Joanna [3 ,4 ,5 ]
Bartel, David P. [3 ,4 ,5 ]
Stoffel, Markus [1 ,2 ]
机构
[1] ETH, Inst Mol Hlth Sci, CH-8093 Zurich, Switzerland
[2] ETH, Competence Ctr Syst Physiol & Metab Dis, CH-8093 Zurich, Switzerland
[3] MIT, Howard Hughes Med Inst, Cambridge, MA 02142 USA
[4] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[5] MIT, Dept Biol, Cambridge, MA 02139 USA
[6] MIT, Computat & Syst Biol Program, Cambridge, MA 02139 USA
基金
美国国家科学基金会;
关键词
MESSENGER-RNAS; IN-VIVO; HEPATOCELLULAR-CARCINOMA; MAMMALIAN MICRORNAS; ENDOGENOUS RNA; GENE; EXPRESSION; IDENTIFICATION; TRANSCRIPTOME; DECREASE;
D O I
10.1016/j.molcel.2014.03.045
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recent studies have reported that competitive endogenous RNAs (ceRNAs) can act as sponges for a microRNA (miRNA) through their binding sites and that changes in ceRNA abundances from individual genes can modulate the activity of miRNAs. Consideration of this hypothesis would benefit from knowing the quantitative relationship between a miRNA and its endogenous target sites. Here, we altered intracellular target site abundance through expression of an miR-122 target in hepatocytes and livers and analyzed the effects on miR-122 target genes. Target repression was released in a threshold-like manner at high target site abundance (>= 1.5 x 10(5) added target sites per cell), and this threshold was insensitive to the effective levels of the miRNA. Furthermore, in response to extreme metabolic liver disease models, global target site abundance of hepatocytes did not change sufficiently to affect miRNA-mediated repression. Thus, modulation of miRNA target abundance is unlikely to cause significant effects on gene expression and metabolism through a ceRNA effect.
引用
收藏
页码:766 / 776
页数:11
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