title: Recognition of RNA duplexes by chemically modified triplex-forming oligonucleotides.
abstract: Triplex is emerging as an important RNA tertiary structure motif, in which consecutive non-canonical base pairs form between a duplex and a third strand. RNA duplex region is also often functionally important site for protein binding. Thus, triplex-forming oligonucleotides (TFOs) may be developed to regulate various biological functions involving RNA, such as viral ribosomal frameshifting and reverse transcription. How chemical modification in TFOs affects RNA triplex stability, however, is not well understood. Here, we incorporated locked nucleic acid, 2-thio U- and 2'-O methyl-modified residues in a series of all pyrimidine RNA TFOs, and we studied the binding to two RNA hairpin structures. The 12-base-triple major-groove pyrimidine-purine-pyrimidine triplex structures form between the duplex regions of RNA/DNA hairpins and the complementary RNA TFOs. Ultraviolet-absorbance-detected thermal melting studies reveal that the locked nucleic acid and 2-thio U modifications in TFOs strongly enhance triplex formation with both parental RNA and DNA duplex regions. In addition, we found that incorporation of 2'-O methyl-modified residues in a TFO destabilizes and stabilizes triplex formation with RNA and DNA duplex regions, respectively. The (de)stabilization of RNA triplex formation may be facilitated through modulation of van der Waals contact, base stacking, hydrogen bonding, backbone pre-organization, geometric compatibility and/or dehydration energy. Better understanding of the molecular determinants of RNA triplex structure stability lays the foundation for designing and discovering novel sequence-specific duplex-binding ligands as diagnostic and therapeutic agents targeting RNA.
authors: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore.
authors: Yuan
authors: Y
authors: Zhou
authors: Elzbieta
authors: E
authors: Kierzek
authors: Zi Ping
authors: ZP
authors: Loo
authors: Meraldo
authors: M
authors: Antonio
authors: Yin Hoe
authors: YH
authors: Yau
authors: York Wieo
authors: YW
authors: Chuah
authors: Susana
authors: S
authors: Geifman-Shochat
authors: Ryszard
authors: R
authors: Kierzek
authors: Gang
authors: G
authors: Chen
mesh_terms: D004247:DNA / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D012330:RNA, Double-Stranded / Q000737:chemistry*; D012965:Sodium Chloride / Q000737:chemistry; D013873:Thionucleotides / Q000737:chemistry; D014529:Uridine / Q000737:chemistry
chemical_list: D009841:Oligonucleotides; D012330:RNA, Double-Stranded; D013873:Thionucleotides; C477371:locked nucleic acid; D012965:Sodium Chloride; D004247:DNA; D014529:Uridine
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