READING 2 BASES TWICE - MAMMALIAN ANTIZYME FRAMESHIFTING IN YEAST

Programmed translational frameshifting is essential for the expression of mammalian ornithine decarboxylase antizyme, a protein involved in the regulation of intracellular polyamines. A cassette containing anti zyme frameshift signals is found to direct high-level (16%) frameshift ing in yeast, Saccharomyces cerevisiae. In contrast to +1 frameshiftin g in the mammalian system, in yeast the same frame is reached by -2 fr ameshifting. Two bases are read twice. The -2 frameshifting is likely to be mediated by slippage of mRNA and re-pairing with the tRNA in the P-site. The downstream pseudoknot stimulates frameshifting by 30-fold compared with 2.5-fold in reticulocyte lysates. When the length of th e spacer between the shift site and the pseudoknot is extended by thre e nucleotides, +1 and -2 frameshifting become equal.