2’-O-Methylribose/Rna Base Fraying Effects And Sensibility To Salt Concentration In Hybrid Duplexes

The 2’-O-methylribose (Nm) is a post-transcriptional modification which results from the addition of a methyl group at the 2’ position of ribose. The stable Nm/RNA hybrids are a natural occurrence in several RNA-related biological processes. The Nm/RNA duplexes are more stable and hybridize faster than in RNA/RNA and DNA/RNA duplexes. The structural change found in Nm is the shift of the C2’/C3’-endo equilibrium, on which the increased stability could depend. X-ray diffraction indicates that the structure of the hybrids is similar to that of RNA/RNA A-type helices. This type of oligonucleotide has been used in RNA probing due to the higher stability and faster hybridization of Nm in comparison to RNA and DNA. The application of mesoscopic models can be useful to evaluate intermolecular interactions, and predict quantities of experimental interest, such as the melting temperature. We applied the Peyrard-Bishop mesoscopic model and obtained its parametrization to Nm/RNA hybrid sequences by using published melting temperatures under low and high salt conditions. Our results show clear base fraying effects. The r(A)/Nm(U) has more stable hydrogen bonds at the terminal position than in the internal counterpart under low salt conditions, which was not observed under high salt conditions. Our results also show an important effect of salt concentration, with a similar hydrogen bond strength for methylation in purine or pyrimidine internal base pairs under high salt conditions.