Abstract

Targeting RNA Structures by Triplex Formation

Gang Chen, Assistant Professor, Nanyang Technological University

The functions of RNA include coding (for protein, RNA, and DNA), gene regulation, catalysis, and immunomodulation. The overall goal of Gang CHEN research group is to better understand the structures and the physical-chemical properties of RNAs and RNA-ligand complexes to provide deeper insight into and to facilitate precise control of the diverse biological functions involving RNA. Naturally-occurring triplexes are important for shaping RNAs into complex three-dimensional architectures and are important for diverse biological functions. As double-stranded RNA stem regions are often involved in biologically important tertiary triplex structure formation and protein binding, the ability to sequence-specifically target any desired RNA duplexes (by triplex formation) would have great potential for biomedical applications. We are developing programmable chemically-modified triplex-forming oligonucleotides (TFOs) and triplex-forming peptide nucleic acids (PNAs) to form TFO•RNA2 and PNA•RNA2 triplexes, respectively. We demonstrate that TFOs and triplex-forming PNAs can specifically bind to minus-one ribosomal frameshift inducing RNA structures, and thus modulate frameshift efficiencies.