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PMID: 7813017 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Autoregulatory frameshifting in decoding mammalian ornithine decarboxylase antizyme.

Cell ·Vol. 80 ·No. 1 ·1995-01-13 ·Pages 51-60

Matsufuji S, Matsufuji T, Miyazaki Y, Murakami Y, Atkins JF, Gesteland RF, Hayashi S

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.

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,metabolism Rats Reading Frames Sequence Deletion
Chemicals
Biogenic Polyamines Codon Ornithine Decarboxylase Inhibitors Proteins RNA, Messenger ornithine decarboxylase antizyme
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Matsufuji S
Howard Hughes Medical Institute, University of Utah, Salt Lake City 84112.
Matsufuji T
Miyazaki Y
Murakami Y
Atkins J F
Gesteland R F
Hayashi S
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
Published
1995-01-13
Pages
51-60
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC7133313
Subset
IM
Grants
NIGMS NIH HHS · R01-GM48152 · United States
Databases
GENBANK
D10706
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