Eukaryotic translation initiation factor 4E-dependent translation is not essential for survival of starved yeast cells

The eukaryotic translation initiation factor 4E (eIF4E) interacts with the mRNA 5 ' cap structure (m(7)GpppX) and is essential for the appropriate tra nslation of the vast majority of eukaryotic mRNAs, Most studies of the yeas t Saccharomyces cerevisiae CDC33 gene product, eIF4E, have been carried out with logarithmically growing cells, and little is known about its role in starved, nonproliferating tells that enter the stationary phase (SP), It ha s previously been found that the rate of translation in SP cells is more th an 2 orders of magnitude lower than it is in dividing yeast cells. Here we show that this low rate of translation is essential for maintaining the via bility of starved yeast cells that enter SP. Specifically, starved cells wh ose eIF4A is inactive or treated with cycloheximide rapidly lose viability. Moreover, after heat inactivation of the cdc33 temperature-sensitive produ ct, the synthesis of most proteins is abolished and only a small group of p roteins is still produced. Unexpectedly, starved cdc33 mutant cells whose e IF4E is inactive and which therefore fail to synthesize the bulk of their p roteins remain viable for long periods of time, indistinguishable from thei r isogenic wild-type counterparts, Taken together, our results indicate tha t eIF4E-independent translation is necessary and sufficient for survival of yeast cells during long periods of starvation.