A synthetic barrel-stave supramolecule with p-oligophenyl “staves” and ß-sheet “hoops” is shown to catalyze the hydrolysis of a doubly labeled homooligomeric model RNA 32 000 times compared to imidazole in water at nanomolar concentrations, 50 °C, and pH 7.0. RNase activity of this rigid-rod ß-barrel is shown to depend on pH (maximal at pH 5.5) and Zn2+ (up to 7-fold increase). Denaturation kinetics suggest that an intact suprastructure is essential for activity and that RNA and Zn2+ exhibit a stabilizing template effect. Product analysis by HPLC is indicative for selective RNase activity with respect to substrate length.