An l-RNA Aptamer with Expanded Chemical Functionality that Inhibits MicroRNA Biogenesis

作者：Kabza Adam M; Sczepanski Jonathan T^*

来源：ChemBioChem, 2017, 18(18): 1824-1827.

DOI：10.1002/cbic.201700362

• l-RNA aptamer
• modified RNA
• molecular evolution
• nucleic acids
• RNA recognition

To facilitate isolation of l-aptamers with novel RNA-binding properties, we employed a cationic nucleotide, 5-aminoallyluridine, during the mirror image in vitro selection process. Through this effort, we identified a modified l-RNA aptamer (MlRA) capable of binding oncogenic precursor microRNA 19a (pre-miR-19a) with exceptional affinity, and we showed that cationic modification is absolutely critical for binding. Furthermore, formation of the MlRA-pre-miR-19a complex inhibited Dicer-mediated cleavage of the pre-miR, thus blocking formation of the mature functional microRNA. The MlRA reported here not only represents the first l-aptamer to be evolved by using modified nucleotides but also the first modified aptamer (of any type) to be selected against a structured RNA target. Our results demonstrate that functionalized l-aptamers, which are intrinsically nuclease-resistant, provide an attractive approach for developing robust RNA-binding reagents.

• 出版日期2017-9-19