Reduced level of the histone deacetylase Sir2 in mRNA decapping mutants leads to silencing defects and premature aging

RNA metabolism directly or indirectly impacts various cellular pathways. Mutations in factors involved in mRNA decapping result in phenotypic markers of apoptosis and lead to premature aging. These traits are accompanied by elevated histone mRNA levels persisting throughout the cell cycle and defects in S-phase progression. Here we show that decapping mutants exhibit low levels of Sir2, which reduces silencing and leads to the elevated transcription of rDNA intergenic spacer regions. We postulate that defects in decapping are associated with the derepression of silencing at heterochromatic-like regions. This, in turn, 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. References [1] Mazzoni C, Falcone C. Biochem Soc Trans. (2011), 39(5):1461-5. Review. [2] Mroczek S & Kufel J (2008).Nucleic Acids Res 36, 2874-2888. [3]Mazzoni C, Herker E, Palermo V, Jungwirth H, Eisenberg T, Madeo F & Falcone C (2005).EMBO Rep 6, 1076-108. [4]Palermo V, Cundari E, Mangiapelo E, Falcone C & Mazzoni C (2010).Cell Cycle 9, 3991-3996. [5] Thompson DM & Parker R (2007).Mol Cell Biol 27, 92-101.