Specific Inhibition of MicroRNA Processing Using L-RNA Aptamers

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.