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

A. D. Branch, H. D. Robertson

Research output: Contribution to journalArticlepeer-review

112 Scopus citations

Abstract

Cis-active ribozymes are potential therapeutic agents; however, to be used in this capacity, they must first be converted to trans-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 efficient and accurate trans cleavage. This work forms the basis for kinetic studies and for adapting the δ ribozymes for cleavage of selected target RNAs.

Original languageEnglish
Pages (from-to)10163-10167
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number22
DOIs
StatePublished - 1991
Externally publishedYes

Keywords

  • RNA structure
  • RNA therapeutics

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