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Programmed frameshifting in the synthesis of mammalian antizyme is +1 in mammals, predominantly +1 in fission yeast, but −2 in budding yeast

  • IVAYLO P. IVANOV (a1), RAYMOND F. GESTELAND (a1) (a2), SENYA MATSUFUJI (a3) and JOHN F. ATKINS (a1) (a2)

Abstract

The coding sequence for mammalian ornithine decarboxylase antizyme is in two different partially overlapping reading frames with no independent ribosome entry to the second ORF. Immediately before the stop codon of the first ORF, a proportion of ribosomes undergo a quadruplet translocation event to shift to the +1 reading frame of the second and main ORF. The proportion that frameshifts is dependent on the polyamine level and, because the product antizyme is a negative regulator of intracellular polyamine levels, the frameshifting acts to complete an autoregulatory circuit by sensing polyamine levels. An mRNA element just 5′ of the shift site and a 3′ pseudoknot are important for efficient frameshifting. Previous work has shown that a cassette with the mammalian shift site and associated signals directs efficient shifting in the budding yeast Saccharomyces cerevisiae at the same codon to the correct frame, but that the shift is −2 instead of +1. The product contains an extra amino acid corresponding to the shift site. The present work shows efficient frameshifting also occurs in the fission yeast, Schizosaccharomyces pombe. This frameshifting is 80% +1 and 20% −2. The response of S. pombe translation apparatus to the mammalian antizyme recoding signals is more similar to that of the mammalian system than to that of S. cerevisiae. S. pombe provides a good model system for genetic studies on the mechanism of at least this type of programmed mammalian frameshifting.

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Corresponding author

Reprint requests to: J.F. Atkins, Department of Human Genetics, University of Utah, 15N, 2030 E, Room 6160, Salt Lake City, Utah 84112-5330, USA; e-mail: john.atkins@genetics.utah.edu.

Keywords

Programmed frameshifting in the synthesis of mammalian antizyme is +1 in mammals, predominantly +1 in fission yeast, but −2 in budding yeast

  • IVAYLO P. IVANOV (a1), RAYMOND F. GESTELAND (a1) (a2), SENYA MATSUFUJI (a3) and JOHN F. ATKINS (a1) (a2)

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