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. 2004 Jul 20;80(1):51–60. doi: 10.1016/0092-8674(95)90450-6

Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme

Senya Matsufuji ∗,†, Tamiko Matsufuji ∗, Youichi Miyazaki †, Yasuko Murakami †, John F Atkins ‡, Raymond F Gesteland ∗,‡, Shin-ichi Hayashi †
PMCID: PMC7133313  PMID: 7813017

Abstract

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.

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