Yeast Lsm Pro-Apoptotic Mutants Show Defects in Autophagy

Abstract

LSM4 is an essential yeast gene encoding a component of different LSM complexes involved in the regulation of mRNA splicing, stability, and translation. In previous papers, we reported that the expression in S. cerevisiae of the K. lactis LSM4 gene lacking the C-terminal Q/N-rich domain in an Lsm4 null strain S. cerevisiae (Sclsm4Δ1) restored cell viability. Nevertheless, in this transformed strain, we observed some phenotypes that are typical markers of regulated cell death, reactive oxygen species (ROS), and oxidated RNA accumulation. In this paper, we report that a similar truncation operated in the S. cerevisiae LSM4 gene confers on cells the same phenotypes observed with the K. lactis lsm4Δ1 gene. Up until now, there was no evidence of the direct involvement of LSM4 in autophagy. Here we found that the Sclsm4Δ1 mutant showed a block in the autophagic process and was very sensitive to nitrogen starvation or treatment with low doses of rapamycin, an inducer of autophagy. Moreover, both during nitrogen starvation and aging, the Sclsm4Δ1 mutant accumulated cytoplasmic autophagy-related structures, suggesting a role of Lsm4 in a later step of the autophagy process.