Magnesium and Nickel metal ions can induce poly(rU)poly(rA)poly(rU) triplexes formation or quadruplexes stabilization

There is a growing appreciation that nucleobases can be used to build supramolecular systems with potential applications, for instance as a scaffold for building synthetic transmembrane ion channels. Besides, recent advances in chemical biology have shown how often non canonical nucleic acids structures (i.e. different from the Watson and Crick double helix form) can play a crucial role in numerous biological processes. We have performed a thermodynamic and kinetic analysis on the ability of magnesium(II) and nickel(II) metal ions to stabilise non-canonical structures of the synthetic RNA poly(rA)poly(rU). It has been found that these cations are both able to induce quadruplex and triplexes formation starting from duplex poly(rA)poly(rU). Which of these forms is prevailing depends on the Mg2+ or Ni2+ concentration. If this is considerably high, the quadruplex structure poly(rU)poly(rA)poly(rU)poly(rA) is stable in solution. On the other hand, below a given metal ion concentration the quadruplex evolves towards a poly(rU)poly(rA)poly(rU) triplex. The mechanistic features of the RNA/metal interaction are qualitatively very similar for the two metal ions. However, they are quantitatively very different as a hundred times lower nickel is necessary to produce the same changes driven by magnesium. The analysis of the results shows that the stabilisation of the quadruplex cannot be explained by electrostatics only. On the basis of previous studies on the poly(A) single strand, it might be supposed that a considerably high metal ion concentration produces dehydration at the polynucleotide that favours strands aggregation.