Role of cytoplasmic deadenylation and mRNA decay factors in yeast apoptosis.

Strains of Saccharomyces cerevisiae lacking factors involved in 5' to 3' mRNA decay pathway (DCP1, DCP2, DHH1, PAT1, LSM1 and LSM4) exhibit caspase-dependent apoptosis and accelerated chronological aging. In the present study, yeast strains lacking mRNA decapping activation factors (DCP2 and LSM1), cytoplasmic exosome function (SKI2) or cytoplasmic deadenylases (double deletion of CCR4 and PAN2) showed typical markers of eukaryotic apoptosis such as increased cellular reactive oxygen species levels, externalization of phosphatidyl serine, chromatin fragmentation, enhanced caspase gene (YCA1) expression and protein activity in mid-log phase cultures. The transcript levels of negative regulators of mRNA decapping (eIF4E and Pab1) were considerably elevated in strains defective in cytoplasmic deadenylation and reduced in strains lacking cytoplasmic 3' to 5' exosome function or decapping activators. Among the yeast strains studied, lsm1Δ and ccr4Δpan2Δ mutants displayed strongest apoptotic phenotype followed by mutants lacking DCP2 or SKI2. Among yeast strains exhibiting deadenylation defects, slight apoptotic phenotype was observed in ccr4Δ mutants and cell death markers imperceptible in pan2Δ mutants.