Association of a peptoid ligand with the apical loop of pri-miR-21 inhibits cleavage by Drosha

作者：Diaz Jason P; Chirayil Rachel; Chirayil Sara; Tom Martin; Head Katie J; Luebke Kevin J^*

来源：RNA-A Publication of the RNA Society, 2014, 20(4): 528-539.

DOI：10.1261/rna.042911.113

• miR-21
• peptoid
• Drosha
• miRNA processing
• RNA hairpin loop

We have found a small molecule that specifically inhibits cleavage of a precursor to the oncogenic miRNA, miR-21, by the microprocessor complex of Drosha and DGCR8. We identified novel ligands for the apical loop of this precursor from a screen of 14,024 N-substituted oligoglycines (peptoids) in a microarray format. Eight distinct compounds with specific affinity were obtained, three having affinities for the targeted loop in the low micromolar range and greater than 15-fold discrimination against a closely related hairpin. One of these compounds completely inhibits microprocessor cleavage of a miR-21 primary transcript at concentrations at which cleavage of another miRNA primary transcript, pri-miR- 16, is little affected. The apical loop of pri-miR-21, placed in the context of pri-miR-16, is sufficient for inhibition of microprocessor cleavage by the peptoid. This compound also inhibits cleavage of pri-miR-21 containing the pri-miR-16 apical loop, suggesting an additional site of association within pri-miR-21. The reported peptoid is the first example of a small molecule that inhibits microprocessor cleavage by binding to the apical loop of a pri-miRNA.

• 出版日期2014-4