GU mismatch stability investigation by a mesoscopic model

The guanine-uracil (GU) mismatch, as well as being the most common base pair after the canonical base pairs CG and AU, plays an important role in RNA by acting as a recognition site for biomolecules. According to Crick, a GU mismatch would be formed by two hydrogen bonds. However, later experimental measurements showed that the stability of this base pair depends on its sequence context. For instance, NMR data indicates that the number of hydrogen bonds varies depending on the GU mismatch flanking base pairs, and when arranged in tandem with another GU also exhibits a dependence on the strand direction. The mesoscopic model proposed by Peyrard and Bishop $^{[1]}$ seems ideal to investigate the stability of GU mismatch due to its ability to distinguish the contribution of stacking interaction and hydrogen bonds. We adapted this model to deal with context-dependent hydrogen bonds of GU mismatches by allowing the parameters to take into account the dependence on the neighbours pairs and strand direction. The optimization of the model parameters was obtained through a set of experimental melting temperatures data $^{[2]}$ by using the technique developed by our group $^{[3,4]}$. As expected, in most contexts the Morse potential obtained for GU mismatches indicate hydrogen bond strengths comparable to AU base pairs. While, in particular, our prediction of a single hydrogen bond for GUpUG tandem configurations agrees with NMR measurements. Our results also suggest that the stability of GU terminal pairs could be attributed to hydrogen bonds as we found that Morse potentials were generally larger than for AU base pairs.

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Funding: CPNq, Capes and Fapemig