Effect of frameshift-inducing mutants of elongation factor 1alpha on programmed +1 frameshifting in yeast.
The translational apparatus very efficiently eliminates errors that would cause a spontaneous shift in frames. The probability of frameshifting can be increased dramatically by either cis or trans-acting factors. Programmed translational frameshift sites are cis-acting sequences that greatly increase the frequency of such errors, at least in part by causing a transient translational pause. Pausing during programmed +1 frameshifts occurs because of slow recognition of the codon following the last read in the normal frame. Frameshifting can also be elevated in strains carrying mutations in the homologous elongation factors EF-Tu in bacteria, and EF-1alpha in the yeast Saccharomyces cerevisiae. This phenotype implies that the factors contribute to frame maintenance. Because EF-Tu/EF-1alpha modulate the kinetics of decoding, it is possible that the frameshift suppressor forms of the factors transiently slow normal decoding, allowing spontaneous frameshifting to occur more efficiently, resulting in phenotypic suppression. We have used a set of frameshift reporter plasmids to test the effect of suppressor forms of EF-1alpha on constructs that differ widely in the efficiency with which they stimulate +1 shifting. When these results were compared to the effect of increased translational pausing, it was apparent that the mutations affecting EF-1alpha do not simply prolong the translational pause. Rather, they appear to generally increase the likelihood of frame errors, apparently by affecting the error correction mechanism of the ribosome.
Farabaugh
P J
PJ
Department of Biological Sciences, University of Maryland Baltimore County, Baltimore 21250, USA. farabaug@umbc.edu
Vimaladithan
A
A
D003062:Codon; D018965:Frameshifting, Ribosomal; D008958:Models, Molecular; D009154:Mutation; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors / Q000737:chemistry / Q000235:genetics*; D018626:Retroelements; D012270:Ribosomes / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*
D003062:Codon; D020648:Peptide Elongation Factor 1; D010445:Peptide Elongation Factors; D018626:Retroelements