The base cleavage specificity of angiogenin toward naturally occurring 
polyribonucleotides has been determined by using rapid RNA sequencing 
technology. With 5S RNAs from Saccharomyces cerevisiae and Escherichia coli, 
angiogenin cleaves phosphodiester bonds exclusively at cytidylic or uridylic 
residues, preferably when the pyrimidines are followed by adenine. However, not 
all of the existent pyrimidine bonds in the 5S RNAs are cleaved, likely owing to 
elements of structure in the substrate. Despite the high degree of sequence 
homology between angiogenin and ribonuclease A (RNase A), which includes all 
three catalytic as well as substrate binding residues, the cleavage patterns 
with natural RNAs are unique to each enzyme. Angiogenin significantly hydrolyzes 
certain bonds that are not appreciably attacked by RNase A and vice versa. The 
different cleavage specificities of angiogenin and RNase A may account for the 
fact that the former is angiogenic while the latter is not.