mRNA degradation in yeast and its effect on cellular lifespan

The steady-state level of cellular mRNA is determined by the rates of synthesis and decay and, for that reason, the control of mRNA degradation is an important component of the regulation of gene expression. In eukaryotes, the decay of mRNAs usually starts with the removal of the 3′ end poly(A) tail. In the yeast Saccharomyces cerevisiae, deadenylation triggers removal of the 5’ mRNA cap structure, a process termed decapping, which is followed 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. 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. We observed that decapping mutants exhibit low levels of Sir2, which reduces silencing and leads to the elevated transcription of rDNA intergenic spacer regions. The observed low level of Sir2 may affect histone modification and induce loss of silencing at specific loci, as well as recombination within rDNA repeats, both of which have been shown to regulate cellular lifespan.