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An l ‐RNA Aptamer with Expanded Chemical Functionality that Inhibits MicroRNA Biogenesis
Author(s) -
Kabza Adam M.,
Sczepanski Jonathan T.
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201700362
Subject(s) - aptamer , dicer , rna , riboswitch , nucleotide , chemistry , microrna , nuclease , systematic evolution of ligands by exponential enrichment , rnase p , non coding rna , biochemistry , computational biology , biology , microbiology and biotechnology , dna , rna interference , gene
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 (M l RA) 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 M l RA–pre‐miR‐19a complex inhibited Dicer‐mediated cleavage of the pre‐miR, thus blocking formation of the mature functional microRNA. The M l RA 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.