Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme.
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.
Matsufuji
S
S
Howard Hughes Medical Institute, University of Utah, Salt Lake City 84112.
Matsufuji
T
T
Miyazaki
Y
Y
Murakami
Y
Y
Atkins
J F
JF
Gesteland
R F
RF
Hayashi
S
S
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015317:Biogenic Polyamines / Q000494:pharmacology*; D003062:Codon; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames; D065108:Ornithine Decarboxylase Inhibitors; D014176:Protein Biosynthesis / Q000187:drug effects; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016364:Reading Frames; D017384:Sequence Deletion
D015317:Biogenic Polyamines; D003062:Codon; D065108:Ornithine Decarboxylase Inhibitors; D011506:Proteins; D012333:RNA, Messenger; C031017:ornithine decarboxylase antizyme