4.8 Article

Specific Inhibition of MicroRNA Processing Using L-RNA Aptamers

Journal

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 137, Issue 51, Pages 16032-16037

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/jacs.5b06696

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Funding

  1. National Institutes of Health [GM065130]

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In vitro selection was used to obtain L-RNA aptamers that bind the distal stem-loop of various precursor microRNAs (pre-miRs). These L-aptamers, termed aptamiRs, bind their corresponding pre-miR target through highly specific tertiary interactions rather than Watson-Crick pairing. Formation of a pre-miR-aptamiR complex inhibits Dicer-mediated processing of the pre-miR, which is required to form the mature functional microRNA. One of the aptamiRs, which was selected to bind oncogenic pre-miR-155, inhibits Dicer processing under simulated physiological conditions, with an IC50 of 87 nM. Given that L-RNAs are intrinsically resistant to nuclease degradation, these results suggest that aptamiRs might be pursued as a new class of miR inhibitors.

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