Since gene silencing by RNA interference (RNAi) has been observed when inexact matches exist in siRNA-mRNA binding, the number of mismatched nucleotides allowed by nature becomes an important quantity in characterizing RNAi specificity. We use scale-free graphs to model the knockdown interactions among different genes and estimate the allowable flexibility by examining transitive RNAi, which amplifies siRNA and cyclically silences targets. Simulation results in
indicate that continually increasing the number of mismatches risks transcriptome-wide knockdown and eventually turns RNAi from defensive to self-destructive. At the phase transition, the number of mismatches indicates a critical value beyond which tRNAi would cause an organism instable. This critical value suggests an upper limit of no more than 6 nt mismatches in the binding.