Twin ribozyme mediated removal of nucleotides from an internal RNA site

Biochem Biophys Res Commun. 2007 Nov 9;363(1):24-9. doi: 10.1016/j.bbrc.2007.08.135. Epub 2007 Aug 31.

Abstract

Over the past two decades, the structure and mechanism of catalytic RNA have been extensively studied; now ribozymes are understood well enough to turn them into useful tools. After we have demonstrated the twin ribozyme mediated insertion of additional nucleotides into a predefined position of a suitable substrate RNA, we here show that a similar type of twin ribozyme is also capable of mediating the opposite reaction: the site-specific removal of nucleotides. In particular, we have designed a twin ribozyme that supports the deletion of four uridine residues from a given RNA substrate. This reaction is a kind of RNA recombination that in the specific context of gene therapy mimics, at the level of RNA, the correction of insertion mutations. As a result of the twin ribozyme driven reaction, 17% of substrate are converted into the four nucleotides shorter product RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Enzyme Activation
  • Genetic Engineering / methods*
  • Nucleotides / chemistry*
  • Nucleotides / genetics
  • RNA / chemistry*
  • RNA / genetics
  • RNA, Catalytic / chemistry*
  • RNA, Catalytic / genetics
  • Recombination, Genetic*

Substances

  • Nucleotides
  • RNA, Catalytic
  • RNA