Loss of Translational Control in Yeast Compromised for the Major mRNA Decay Pathway

Abstract

The cytoplasmic fate of mRNAs is dictated by the relative activities of the intimately connected mRNA decay and translation initiation pathways. In this study, we have found that yeast strains compromised for stages downstream of deadenylation in the major mRNA decay pathway are incapable of inhibiting global translation initiation in response to stress. In the past, the paradigm of the eIF2α kinase-dependent amino acid starvation pathway in yeast has been used to evaluate this highly conserved stress response in all eukaryotic cells. Using a similar approach we have found that even though the mRNA decay mutants maintain high levels of general translation, they exhibit many of the hallmarks of amino acid starvation, including increased eIF2α phosphorylation and activated GCN4 mRNA translation. Therefore, these mutants appear translationally oblivious to decreased ternary complex abundance, and we propose that this is due to higher rates of mRNA recruitment to the 40S ribosomal subunit.

This work was supported largely by Wellcome Trust project grant 061867/Z/00/Z to M.P.A. L.E.A.H. is supported by an MRC studentship. S.G.C. is supported by Wellcome Trust project grant 067328/Z/02/Z to M.P.A. In addition, the work was supported by NIH grant GM50308 to A.B.S. and by an EMBO long-term fellowship to M.P.A. while at University of California at Berkeley.

We thank G. Pavitt, C. Grant, A. Johnson, C. Wilutz, S. Peltz, S. Butler, and P. Linder for reagents and advice. We especially thank R. Parker for his generous donation of yeast strains and plasmids, without which this work would not have been possible.