Hydrolytic stability of helical RNA: a selective advantage for the natural 3',5'-bond.

Dodecaadenylic acid containing a single 2', 5'-linkage at a defined position was formed by the coupling of two hexamers on a poly(U) template at 2 degrees. The rate of hydrolysis of this dodecamer was compared with that of a dodecamer that contained only the natural 3', 5'-linkages. At 40 degrees, in 1 M aqueous ethylenediamine at pH 8 in the absence of poly(U), both dodecamers hydrolyzed at comparable rates, but the addition of two equivalents of poly(U) caused a 7-fold increase in the initial rate of hydrolysis of the oligomer containing the 2', 5'-bond, and a 5-fold decrease in the initial rate of hydrolysis of the natural oligomer. When the oligomers are fully constrained in helical form, the ratio of the rates of cleavage of one 2', 5'-bond to one 3', 5'-bond under these conditions is probably about 900:1. The use of the 3', 5'-bond, in combination with a right-handed helix, appears to have had a large selective advantage over the use of the 2', 5'-bond for the storage of genetic information.