Efficient trans cleavage and a common structural motif for the ribozymes of the human hepatitis δ agent

Cis-active ribozymes are potential therapeutic agents; however, to be used in this capacity, they must first be converted to trails-active ribozymes, a process facilitated by analysis of their structures. We present evidence that the genomic and antigenomic ribozymes of the human δ hepatitis agent share a structural ("axehead") motif that has conserved sequence elements and a stable hairpin. Guided by the features of the axehead, we divided each of the δ ribozymes into two subdomains, which we synthesized as separate RNA transcripts to give an enzyme and substrate for each ribozyme. Incubation of a substrate subdomain with its matching enzyme resulted in officient and accurate trans cleavage. This work forms the basis for kinetic studies and for adapting the δ ribozymes for cleavage of selected target RNAs. (.