a b s t r a c tWe have engineered a self-processing RNA, derived from the hairpin ribozyme that runs through a cascade of cleavage and ligation reactions thereby changing its topology. The first two cleavage events leave the resulting RNA with a 5 0 -OH group and a 2 0 ,3 0 -cyclic phosphate. Thus, upon refolding, intramolecular ligation delivers a cyclic species. In addition, we demonstrate formation of concatemers resulting from multiple intermolecular ligations. Our results demonstrate the potential of RNA for self-supported topology changes and support the suggestion of 2 0 ,3 0 -cyclic phosphates being suitable activated building blocks for reversible phosphodiester bond formation in the RNA world.