Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme

Cell. 1995 Jan 13;80(1):51-60. doi: 10.1016/0092-8674(95)90450-6.


Rat antizyme gene expression requires programmed, ribosomal frameshifting. A novel autoregulatory mechanism enables modulation of frameshifting according to the cellular concentration of polyamines. Antizyme binds to, and destabilizes, ornithine decarboxylase, a key enzyme in polyamine synthesis. Rapid degradation ensues, thus completing a regulatory circuit. In vitro experiments with a fusion construct using reticulocyte lysates demonstrate polyamine-dependent expression with a frameshift efficiency of 19% at the optimal concentration of spermidine. The frameshift is +1 and occurs at the codon just preceding the terminator of the initiating frame. Both the termination codon of the initiating frame and a pseudoknot downstream in the mRNA have a stimulatory effect. The shift site sequence, UCC-UGA-U, is not similar to other known frameshift sites. The mechanism does not seem to involve re-pairing of peptidyl-tRNA in the new frame but rather reading or occlusion of a fourth base.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biogenic Polyamines / pharmacology*
  • Codon
  • DNA Mutational Analysis
  • Frameshift Mutation*
  • Gene Expression Regulation*
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Open Reading Frames
  • Ornithine Decarboxylase Inhibitors*
  • Protein Biosynthesis / drug effects
  • Proteins / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Reading Frames
  • Sequence Deletion


  • Biogenic Polyamines
  • Codon
  • Ornithine Decarboxylase Inhibitors
  • Proteins
  • RNA, Messenger
  • ornithine decarboxylase antizyme

Associated data

  • GENBANK/D10706