A truncated form of KlLsm4p and the absence of factors involved in mRNA decapping trigger apoptosis in yeast.
The LSM4 gene of Saccharomyces cerevisiae codes for an essential protein involved in pre-mRNA splicing and also in mRNA decapping, a crucial step for mRNA degradation. We previously demonstrated that the first 72 amino acids of the Kluyveromyces lactis Lsm4p (KlLsm4p), which contain the Sm-like domains, can restore cell viability in both K. lactis and S. cerevisiae cells not expressing the endogenous protein. However, the absence of the carboxy-terminal region resulted in a remarkable loss of viability in stationary phase cells (). Herein, we demonstrate that S. cerevisiae cells expressing the truncated LSM4 protein of K. lactis showed the phenotypic markers of yeast apoptosis such as chromatin condensation, DNA fragmentation, and accumulation of reactive oxygen species. The study of deletion mutants revealed that apoptotic markers were clearly evident also in strains lacking genes involved in mRNA decapping, such as LSM1, DCP1, and DCP2, whereas a slight effect was observed in strains lacking the genes DHH1 and PAT1. This is the first time that a connection between mRNA stability and apoptosis is reported in yeast, pointing to mRNA decapping as the crucial step responsible of the observed apoptotic phenotypes.
Mazzoni
Cristina
C
Pasteur Institute-Cenci Bolognetti Foundation, Department of Cell and Developmental Biology, University of Rome, Italy. cristina.mazzoni@uniroma1.it
Mancini
Patrizia
P
Verdone
Loredana
L
Madeo
Frank
F
Serafini
Agnese
A
Herker
Eva
E
Falcone
Claudio
C
D000483:Alleles; D017209:Apoptosis; D002843:Chromatin / Q000378:metabolism; D053487:DEAD-box RNA Helicases; D053938:DNA Fragmentation; D004268:DNA-Binding Proteins / Q000235:genetics; D017353:Gene Deletion; D005838:Genotype; D020287:In Situ Nick-End Labeling; D007716:Kluyveromyces / Q000378:metabolism; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D010641:Phenotype; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D020365:RNA Helicases / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
D002843:Chromatin; D004268:DNA-Binding Proteins; C103266:PAT1 protein, S cerevisiae; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D029701:Saccharomyces cerevisiae Proteins; D012313:RNA; C445083:DHH1 protein, S cerevisiae; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases