AUTOREGULATORY FRAMESHIFTING IN DECODING MAMMALIAN ORNITHINE DECARBOXYLASE ANTIZYME

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