In addition to using the full A3A signature sequences, the probability of mutagenesis should not be solely based on nucleotide sequence, but should also be weighted by the propensity of the target sequence to be within a structured loop. Secondary structure prediction software could be used to identify the consensus sequence in loop regions of structured DNA or RNA. A3A signature sequences that we identified, (T/C)TC(A/G), not only account for the discrepancies in the A3A target sequences reported in the literature such as TTCA versus CTCG20,21, but also lead us to advocate a new paradigm for identifying A3A’s involvement in mutation of endogenous or exogenous DNA.