Two RNA Folds from One Sequence: A Ribozyme with Versatile Substrate Processing Abilities

We report the design of a single RNA sequence capable of adopting one of two ribozyme folds and catalyzing the cleavage and/or ligation of the respective substrates. The RNA is able to change its conformation in response to its environment, hence it is called chameleon ribozyme (CHR). Efficient RNA cleavage of two different substrates as well as RNA ligation by CHR is demonstrated in separate experiments and in a one pot reaction. Our study shows that sequence variants of the hairpin ribozyme intersect with the hammerhead ribozyme and that rather short RNA molecules can have comprehensive conformational flexibility, which is an important feature for the emergence of new functional folds in early evolution. Sequence variants of the hairpin ribozyme can adopt a hammerhead fold, allowing them to process various substrates by utilizing their inherent activity and comprehensive conformational flexibility to support RNA cleavage and ligation. image