mRNA degradation and its effect on cellular lifespan and apoptosis in yeast

The steady-state level of cellular mRNA is the result of the equilibrium between the rates of synthesis and decay. For this reason, the control of mRNA degradation is an important element in regulation of gene expression. In all eukaryotes, the decay of mRNAs usually starts with the removal of the 3′ end poly(A) tail. In the principal degradation pathway in the yeast S. cerevisiae, deadenylation is followed by decapping and by 5′ to 3′ mRNA degradation by the exonuclease Xrn1. mRNA decay can be also carried out in the opposite direction by the exosome, a complex with a 3′ to 5′ nuclease activity. We previously reported that yeast mutants in genes of the mRNA decapping pathway show premature aging and undergo apoptosis by a YCA1-dependent pathway. These traits are accompanied by elevated histone mRNA levels persisting throughout the cell cycle and defects in S-phase progression. Analyzing the data concerning the negative genetic interactions of specific genes, as well those obtained with genome wide analysis, we found that gene mutants that are lethal/sick with lsm genes can be clustered in functional groups such as histone/chromatine modifications, protein translation, DNA replication/repair, nuclear mRNA export, mitochondrial function/biogenesis and autophagy. We are currently studying the role of these pathways in cellular aging and apoptosis.