Cristina Mazzoni, Vanessa Palermo and Claudio Falcone
The steady-state level of cellular mRNA is the result of the equilibriumbetween 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 yeast Saccharomyces 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. Recent studies have established yeasts as model to study the mechanisms and the regulation of apoptosis. The YCA1 gene codes for a metacaspase and many apoptotic responses pass through the activation of this protease. AIF1 and NUC1, encode mitochondrial proteins, homologues to the mammalian Aif and EndoG, respectively, that following apoptotic stimuli move from mitochondria to the nucleus and promote cell death. In our laboratory we demonstrated 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. It has been demonstrated that, beside coding mRNAs, RNA polymerase II also transcribes for non coding RNA that could have regulatory roles. These transcripts are degraded by a variety of different mechanisms, including exosome, cytoplasmic decapping and 5-to-3 decay, and nonsense-mediated decay. Analyzing the data concerning the negative genetic interactions of specific genes, as well those obtained with genome, we found that a large group of gene mutants that are lethal/sick with lsm genes belongs tohistone/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.