How RNA folds

We describe the RNA folding problem and contrast it with the much more diff icult protein folding problem. RNA has four similar monomer units, whereas proteins have 20 very different residues. The folding of RNA is hierarchica l in that secondary structure is much more stable than tertiary folding. In RNA the two levels of folding (secondary and tertiary) can be experimental ly separated by the presence or absence of Mg2+. Secondary structure can be predicted successfully from experimental thermodynamic data on secondary s tructure elements: helices, loops, and bulges. Tertiary interactions:can :t hen be added without much distortion of the secondary structure. These obse rvations suggest a folding algorithm to predict the structure of an RNA fro m its sequence. However, to solve the RNA folding problem one needs thermod ynamic data on tertiary structure interactions, and identification and char acterization of metal-ion binding sites. These data, together with force ve rsus extension measurements on single RNA molecules, should provide the inf ormation necessary to test and refine the proposed algorithm. (C) 1999 Acad emic Press.