Role of cytoplasmic deadenylation and mRNA decay factors in yeast apoptosis

• Published in: FEMS yeast research 2015-03, Vol.15 (2)
• Main Authors: Raju, Kalidindi K., Natarajan, Sumathi, Kumar, N. Sunil, Kumar, D. Anil, NM, Raghavendra
• Format: Article
• Language: English
• Subjects: Aging; Apoptosis; Caspase; Cell death; Chromatin; Clonal deletion; Gene Deletion; Initiation factor eIF-4E; Metabolic Networks and Pathways - genetics; mRNA turnover; Mutants; Phenotypes; Reactive oxygen species; RNA Stability; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae - physiology; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Serine; Transcription; Yeast
• ISSN: 1567-1356; 1567-1364
• DOI: 10.1093/femsyr/fou006

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. The Strong apoptotic phenotype observed in the double mutants of CCR4/PAN2 suggests role of ploy(A) tail length control in caspase-dependent apoptotic cell death in strains with defects in cytoplasmic deadenylation and Changes in transcript abundance of eIF4E and Pab1 in strains defective in deadenylation (ccr4Δ and), decapping (dcp2Δ and lsm1Δ strains) or cytoplasmic exosome function (ski2Δ) suggest decapping antagonists contribute to stress responses accompanying enhanced cell death.