Molecular Genetics and Genomics

, Volume 282, Issue 1, pp 83–96

The paradox of viable sup45 STOP mutations: a necessary equilibrium between translational readthrough, activity and stability of the protein

Authors

  • Denis Kiktev
    • Department of Genetics and BreedingSt Petersburg State University
  • Svetlana Moskalenko
    • Department of Genetics and BreedingSt Petersburg State University
  • Olga Murina
    • Department of Genetics and BreedingSt Petersburg State University
  • Agnès Baudin-Baillieu
    • UMR 8621, IGMUniv Paris-Sud
  • Jean-Pierre Rousset
    • UMR 8621, IGMUniv Paris-Sud
    • Department of Genetics and BreedingSt Petersburg State University
Original Paper

DOI: 10.1007/s00438-009-0447-5

Cite this article as:
Kiktev, D., Moskalenko, S., Murina, O. et al. Mol Genet Genomics (2009) 282: 83. doi:10.1007/s00438-009-0447-5

Abstract

The mechanisms leading to non-lethality of nonsense mutations in essential genes are poorly understood. Here, we focus on the factors influencing viability of yeast cells bearing premature termination codons (PTCs) in the essential gene SUP45 encoding translation termination factor eRF1. Using a dual reporter system we compared readthrough efficiency of the natural termination codon of SUP45 gene, spontaneous sup45-n (nonsense) mutations, nonsense mutations obtained by site-directed mutagenesis (76Q → TAA, 242R → TGA, 317L → TAG). The nonsense mutations in SUP45 gene were shown to be situated in moderate contexts for readthrough efficiency. We showed that readthrough efficiency of some of the mutations present in the sup45 mutants is not correlated with full-length Sup45 protein amount. This resulted from modification of both sup45 mRNA stability which varies 3-fold among sup45-n mutants and degradation rate of mutant Sup45 proteins. Our results demonstrate that some substitutions in the place of PTCs decrease Sup45 stability. The viability of sup45 nonsense mutants is therefore supported by diverse mechanisms that control the final amount of functional Sup45 in cells.

Keywords

Translation terminationNonsensePTCProtein stabilitySup45eRF1[PSI+]

Copyright information

© Springer-Verlag 2009