(A) Chemical structures of adenosine, 2,6-diaminopurine (DAP), guanosine, and inosine (I) nucelobases. Hydrogen bond donors highlighted in blue; hydrogen bond acceptors highlighted in pink. (B) t1I target RNA omit map contoured at 3σ (grey mesh). No electron density was observed for t1I. (C) t1DAP target RNA omit map contoured at 3σ (grey mesh). Clear electron density was observed for t1DAP. (D) Plot of target bound vs Ago2-guide concentration for t1A, t1I, t1DAP, and t1m6A target RNAs.