Multifaceted physiological response allows yeast to adapt to the loss of the signal recognition particle-dependent protein-targeting pathway

Translational control has recently been recognized as an important facet of adaptive responses to various stress conditions. We describe the adaptatio n response of the yeast Saccharomyces cerevisiae to the loss of one of two mechanisms to target proteins to the secretory pathway. Using inducible mut ants that block the signal recognition particle (SRP) pathway, we find that cells demonstrate a physiological response to the loss of the SRP pathway that includes specific changes in global gene expression. Upon inducing the loss of the SRP pathway, SRP-dependent protein translocation is initially blocked, and cell growth is considerably slowed. Concomitantly, gene expres sion changes include the induction of heat shock genes and the repression o f protein synthesis genes. Remarkably, within hours, the efficiency of prot ein sorting improves while cell growth remains slow in agreement with the p ersistent repression of protein synthesis genes. Our results suggest that h eat shock gene induction serves to protect cells from mislocalized precurso r proteins in the cytosol, whereas reduced protein synthesis helps to regai n efficiency in protein sorting by reducing the load on the protein translo cation apparatus. Thus, we suggest that cells trade speed in cell growth fo r fidelity in protein sorting to adjust to life without SRP.