Structure folding of RNA kissing complexes in salt solutions: predicting 3D structure, stability, and folding pathway

RNA kissing complexes are essential for genomic RNA dimerization and regulation of gene expression, and their structures and stability are critical to their biological functions. In this work, we used our previously developed coarse-grained model with an implicit structure-based electrostatic potential to predict three-dimensional (3D) structures and stability of RNA kissing complexes in salt solutions. For extensive RNA kissing complexes, our model shows great reliability in predicting 3D structures from their sequences, and our additional predictions indicate that the model can capture the dependence of 3D structures of RNA kissing complexes on monovalent/divalent ion concentrations. Moreover, the comparisons with extensive experimental data show that the model can make reliable predictions on the stability for various RNA kissing complexes over wide ranges of monovalent/divalent ion concentrations. Notably, for RNA kissing complexes, our further analyses show the important contribution of coaxial stacking to the 3D structures and stronger stability than the corresponding kissing-interface duplexes at high salts. Furthermore, our comprehensive analyses for RNA kissing complexes reveal that the thermally folding pathway for a complex sequence is mainly determined by the relative stability of two possible folded states of kissing complex and extended duplex, which can be significantly modulated by its sequence.