Scientists in Japan are thinking positively. A team led by Naoki Sugimoto at Konan University in Kobe is studying the role of cations in nucleic acid folding.

DNA and RNA folding controls many biological systems, for example the switching on and off of some genes. However, the process is not well understood - including the role of cation binding to the nucleic acids.

Cation binding shields the nucleic acids' negatively charged phosphate groups, allowing their closer approach on folding. Measuring a cation's binding affinity to short lengths of nucleic acid called oligonucleotides gives crucial insights into the cation's energetic contributions to folding. But obtaining quantitative measurements of these affinities is difficult, due to the many energy changes occurring during the folding process. Now, Sugimoto's team has developed a technique to overcome this problem.

Using a straightforward gel electrophoresis method, the researchers can study the equilibrium between folded (hairpin) and unfolded (dimer) oligonucleotides. By monitoring the effects of different cations on the equilibrium, the group has measured the cations' binding affinities during folding. These provide vital information for understanding fundamental aspects of oligonucleotide interactions, and in particular DNA and RNA folding into dimers, suggest the researchers.

Hairpin loops of DNA unfold when the cation concentration is increased

Philip Bevilacqua, head of the RNA folding, catalysis and protein interactions research group at Pennsylvania State University, University Park, US, said that 'the ability of physiological salts to induce RNA dimerisation is a result of potentially great importance in biology. These data show that physiological salts, especially polyvalent ones, will be adept at causing RNAs to refold into dimer forms, which may have profound biological implications.'

Sugimoto said that he hopes the work will add important missing data to the field and lead to new breakthroughs in biochemistry. 'Our experimental technique, which is simple and widely applicable, can be used for diffusely bound cations bound even very weakly. Our research is ongoing to quantify their contributions and construct an interaction energy database of nucleic acids to realise tailor-made biochemistry - the aim of our institute,' he said.

Edward Morgan