Recognition of RNA Sequence and Structure by Duplex and Triplex Formation: Targeting miRNA and Pre-miRNA

Abstract

RNAs form complex structures containing both single-stranded (ss) and double-stranded (ds) regions for their diverse regulatory and catalytic functions. The emerging RNA sequence and structure databases provide the foundation for developing RNA-binding ligands for reprogramming RNA–RNA and RNA–protein interactions through the recognition of RNA sequence and structure. We choose miRNA biogenesis and gene regulation pathways as examples to summarize how chemically modified nucleic acid oligomers can be used to target specific RNA sequences and structures through duplex and triplex formation. We discuss the significant progress that has been made in using anti-miRNA oligonucleotides in targeting mature miRNA by duplex formation. The strategy of targeting dsRNA by triplex formation is relatively less explored. We summarize the recent results of developing nucleobase and backbone modifications in peptide nucleic acids (PNAs) to facilitate structure-specific and selective targeting of dsRNAs over ssRNA and dsDNA at physiological conditions. We briefly discuss how sequence-specific dsRNA-binding PNAs may be utilized to target disease-associated miRNA precursors and viral RNAs.