The phosphodiester bonds in the covalent backbone of
RNA are subject to slow, non-enzymatic cleavage through the “in-line” nucleophilic
attack of the 2´ oxygen on the adjacent phosphorus center (see Fig. 1).
When the 2´ oxygen, the phosphorus, and adjacent 5´ oxygen enter an “inline”
conformation, the 2´ oxygen acts as a nucleophile in the intramolecular
displacement of the 5´ oxygen in the adjacent phosphorus center and efficiently
cleaves the RNA linkage. The relative speeds of spontaneous cleavage are
dependent on local structural characteristics of each RNA linkage (see Fig. 2).
Single-stranded RNA lacks secondary structure and is free to sample a range