title: tRNA Shifts the G-quadruplex-Hairpin Conformational Equilibrium in RNA towards the Hairpin Conformer.
abstract: Non-coding RNAs play important roles in cellular homeostasis and are involved in many human diseases including cancer. Intermolecular RNA-RNA interactions are the basis for the diverse functions of many non-coding RNAs. Herein, we show how the presence of tRNA influences the equilibrium between hairpin and G-quadruplex conformations in the 5' untranslated regions of oncogenes and model sequences. Kinetic and equilibrium analyses of the hairpin to G-quadruplex conformational transition of purified RNA as well as during co-transcriptional folding indicate that tRNA significantly shifts the equilibrium toward the hairpin conformer. The enhancement of relative translation efficiency in a reporter gene assay is shown to be due to the tRNA-mediated shift in hairpin-G-quadruplex equilibrium of oncogenic mRNAs. Our findings suggest that tRNA is a possible therapeutic target in diseases in which RNA conformational equilibria is dysregulated.
authors: Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
authors: Ambadas B
authors: AB
authors: Rode
authors: Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
authors: Tamaki
authors: T
authors: Endoh
authors: Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan. sugimoto@konan-u.ac.jp.
authors: Naoki
authors: N
authors: Sugimoto
mesh_terms: D020121:5' Untranslated Regions; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D007700:Kinetics; D009690:Nucleic Acid Conformation; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020121:5' Untranslated Regions; D012333:RNA, Messenger; D012343:RNA, Transfer
keywords: G-quadruplex; conformational transition; equilibrium shift; hairpin structure; tRNA