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

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. We previously reported that yeast mutants in genes of the mRNA decapping pathway show premature aging and undergo programmed cell death. 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 related to mRNA turn over.