Article

Silencing of microRNAs in vivo with “antagomiRs”

Laboratory of RNA Molecular Biology, The Rockefeller University, New York, New York, United States
Nature (Impact Factor: 41.46). 01/2006; 438(7068):685-9. DOI: 10.1038/nature04303
Source: PubMed

ABSTRACT

MicroRNAs (miRNAs) are an abundant class of non-coding RNAs that are believed to be important in many biological processes through regulation of gene expression. The precise molecular function of miRNAs in mammals is largely unknown and a better understanding will require loss-of-function studies in vivo. Here we show that a novel class of chemically engineered oligonucleotides, termed 'antagomirs', are efficient and specific silencers of endogenous miRNAs in mice. Intravenous administration of antagomirs against miR-16, miR-122, miR-192 and miR-194 resulted in a marked reduction of corresponding miRNA levels in liver, lung, kidney, heart, intestine, fat, skin, bone marrow, muscle, ovaries and adrenals. The silencing of endogenous miRNAs by this novel method is specific, efficient and long-lasting. The biological significance of silencing miRNAs with the use of antagomirs was studied for miR-122, an abundant liver-specific miRNA. Gene expression and bioinformatic analysis of messenger RNA from antagomir-treated animals revealed that the 3' untranslated regions of upregulated genes are strongly enriched in miR-122 recognition motifs, whereas downregulated genes are depleted in these motifs. Analysis of the functional annotation of downregulated genes specifically predicted that cholesterol biosynthesis genes would be affected by miR-122, and plasma cholesterol measurements showed reduced levels in antagomir-122-treated mice. Our findings show that antagomirs are powerful tools to silence specific miRNAs in vivo and may represent a therapeutic strategy for silencing miRNAs in disease.

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Available from: Jan Krützfeldt, Jan 03, 2016
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    • "MiR-31 significantly inhibited luciferase activity in cells transfected with TRADD-Luc, but not in cells transfected with CT- Luc (Figure 2C). AntagomiRs are chemically modified oligonucleotides that bind to and inhibit the functions of miRs[20]. U251 miR-31 (+) cells were transfectedFigure 2D). "
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