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ACS Chem Biol. 2013 May 17;8(5):930-8. doi: 10.1021/cb300650y. Epub 2013 Mar 6.

A molecular-beacon-based screen for small molecule inhibitors of miRNA maturation.

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1
Proteomics and Structural Biology Unit CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India.

Abstract

miRNAs are small non-coding RNAs that regulate about 60% of mammalian genes by modulating their transcript levels. Network scale studies of miRNA-mediated regulatory circuits demonstrate the central importance of this class of small RNA in the maintenance of biological robustness. More recently, several reports have described the deregulation of numerous miRNA to be causally associated with many diseases, including cancer. These studies have highlighted the potential for development of therapeutic modalities against miRNA. Previous screening protocols, for small molecules targeting miRNA function, are either costly or technically too complex to be applied in a high-throughput manner in standard chemical laboratories. We describe a simple in vitro screening method using a DNA-based molecular beacon that overcomes the limitations associated with earlier screens. We used this method to identify inhibitors of miR-27a function from a library of 14 aminoglycosides as a pilot study. Inhibitory molecules identified were further scrutinized to identify the validity of screen. With this proof of concept we illustrate the utility of a scalable molecular-beacon-based screening strategy for miRNA inhibitors.

PMID:
23402670
DOI:
10.1021/cb300650y
[Indexed for MEDLINE]
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