RNAs are surprisingly adept at folding into specific shapes capable of
ligand recognition and catalysis. Thermodynamic analysis of the unfol
ding of several different RNAs suggests that there are at least three
strategies an RNA might use to achieve a very stable and compactly fol
ded structure: hydrogen bonding between irregular complementary surfac
es (as in transfer RNA tertiary structure); monovalent and divalent io
ns bound to specific sites (as found in a ribosomal RNA fragment) and
pseudoknot folds (exemplified by a messenger RNA fragment with extensi
ve noncanonical structure).