tRNA Shifts the G‐quadruplex–Hairpin Conformational Equilibrium in RNA towards the Hairpin Conformer

AbstractNon‐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.