An aptamer targeting the apical-loop domain modulates pri-miRNA processing

MicroRNAs are short non-coding RNAs that recognize complementary bases on target mRNAs thereby triggering either inhibition of translation initiation or mRNA degradation. They have unique expression patterns and are involved in almost every important biological process, including cell proliferation, differentiation, and apoptosis. In turn, deregulation of miRNA expression patterns is a key condition in the onset and progression of tumour development.
Due to the prominent role of miRNAs in regulating gene expression, considerable efforts have been placed to develop selective tools that will allow direct targeting of miRNAs affecting either their biogenesis or function. Here, we introduce another class of nucleic acid-based molecular tools to interfere with miRNA activity, namely RNA aptamers that specifically recognize the loop-domains of a pri-miRNA and modulate its processing. We describe the isolation and characterisation of an RNA aptamer that specifically targets the pri-miRNA polycistron 17~18a~19a~20a~19b-1~92, and show that the aptamer binds inter alia to the apical-loop domain of pri-miR18a and thereby inhibits the biogenesis of all miRNAs 17-19b-1 within this cluster. Our results show that aptamers can be applied as agents that modulate pri-miRNA processing and as tools for elucidating mechanisms of this process. Furthermore, the ability to modulate miRNA-maturation by targeting the apical-loop domain underlines the importance of these domains during pri-miRNA processing.