A Slow Dynamic RNA Switch Regulates Processing of microRNA-21

The microRNAs are non-coding RNAs which post-transcriptionally regulate the expression of many eukaryotic genes, and whose dysregulation is a driver of human disease. Here we report the discovery of a very slow (0.1 s(-1)) conformational rearrangement at the Dicer cleavage site of pre-miR-21, which regulates the relative concentration of readily-and inefficiently-processed RNA structural states. We show that this dynamic switch is affected by single nucleotide mutations and can be biased by small molecule and peptide ligands, which can direct the microRNA to occupy the inefficiently processed state and reduce processing efficiency. This result reveals a new mechanism of RNA regulation and suggests a chemical approach to suppressing or activating pathogenic microRNAs by selective stabilization of their unprocessed or processed states. Published by Elsevier Ltd.

Automated summary

This study reveals a new mechanism of RNA regulation, showing that the conformational rearrangement at the Dicer cleavage site of pre-miR-21 can regulate the processing efficiency of microRNA. By manipulating this dynamic switch, it is possible to selectively stabilize the unprocessed or processed states of pathogenic microRNAs, providing a potential chemical approach for their suppression or activation.