458 research outputs found
Reduced level of the histone deacetylase Sir2 in mRNA decapping mutants leads to silencing defects and premature aging
No full textRNA 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
Attività di ricerca e formazione tra Pisa e Damasco, Italia Siria. Il progetto del castello di Harim
No full textNel periodo settembre-ottobre del 1999 e 2000 Nicola Santopuoli, organizza e dirige in accordo con la Direzione Generale alle Antichità della Siria, l’Università di Venezia (prof. S. Gelichi), l’Università di Pisa (prof. C. Arias e prof.ssa S. Mazzoni) uno stage nel sito archeologico di Harim con studenti della Facoltà di Architettura di Ferrara, laureati della Facoltà di Architettura di Aleppo, architetti della Direzione Generale alle Antichità della Siria e diplomati della Scuola del Restauro del Mosaico di Ravenna. Il gruppo ha lavorato in stretta interazione con la spedizione archeologica diretta dal prof. S. Gelichi e si è occupato del rilievo, dello studio e del restauro del castello di Harim situato sulla sommità di un tell nella vallata dell’Oronte vicino al confine turco. I risultati della campagna di rilievo sono stati pubblicati nel volume ed esposti in una mostra promossa dall’ambasciata italiana di Damasco e organizzata dalla Missione Archeologica Italiana presso l’Università di Damasco
External and internal triggers of cell death in yeast
No full textIn recent years, yeast was confirmed as a useful eukaryotic model system to decipher the complex mechanisms and networks occurring in higher eukaryotes, particularly in mammalian cells, in physiological as well in pathological conditions. This article focuses attention on the contribution of yeast in the study of a very complex scenario, because of the number and interconnection of pathways, represented by cell death. Yeast, although it is a unicellular organism, possesses the basal machinery of different kinds of cell death occurring in higher eukaryotes, i.e., apoptosis, regulated necrosis and autophagy. Here we report the current knowledge concerning the yeast orthologs of main mammalian cell death regulators and executors, the role of organelles and compartments, and the cellular phenotypes observed in the different forms of cell death in response to external and internal triggers. Thanks to the ease of genetic manipulation of this microorganism, yeast strains expressing human genes that promote or counteract cell death, onset of tumors and neurodegenerative diseases have been constructed. The effects on yeast cells of some of these genes are also presented
Isolation and study of KlLSM4, a Kluyveromyces lactis gene homologous to the essential gene LSM4 of Saccharomyces cerevisiae.
No full textWe have isolated the KlLSM4 gene as a multicopy suppressor of a Kluyveromyces lactis mutant which shows a rag(-) phenotype (resistance to antimycin A on glucose). This gene is homologous to the ScLSM4 of Saccharomyces cerevisiae, which codes for an essential 187 amino acid protein containing Sm-like domains. These motifs are present in the evolutionarily conserved family of the Sm-like proteins, which are involved in a large number of cellular processes, including pre-mRNA splicing and mRNA decapping. We demonstrated that the first 72 amino acids of KlLsm4p, which contain the Sm-like domains, can restore cell viability in both K. lactis and S. cerevisiae cells lacking the wild-type protein. However, the absence of the carboxy-terminal region resulted in a remarkable loss of cell viability in the stationary phase. The KlLSM4 sequence has been deposited in the EMBL Data library under Accession No. AJ311719
RNA stability and metabolism in regulated cell death, aging and diseases
No full textThe stability of RNAs represents a crucial point for cell life in that these molecules code for proteins and also play structural and regulatory functions. In this review, we will mainly focus on RNA stability and its connection with cell death and aging. In addition, we will consider the interaction of RNAs with ribonucleoprotein complexes, such as P-bodies and stress granules, as well as the role of non-coding RNAs. Finally, we will mention some correlations between RNA and diseases, considering yeast as a simple model system for the study of human cancer and neurodegenerative disorders
Caspase-dependent apoptosis in yeast
No full textDamaging environment, certain intracellular defects or heterologous expression of pro-apoptotic genes induce death in yeast cells exhibiting typical markers of apoptosis. In mammals, apoptosis can be directed by the activation of groups of proteases, called caspases, that cleave specific substrates and trigger cell death. In addition, in plants, fungi, Dictyostelium and metazoa, paracaspases and metacaspases have been identified that share some homologies with caspases but showing different substrate specificity. In the yeast Saccharomyces cerevisiae, a gene (MCA1/YCA1) has been identified coding for a metacaspase involved in the induction of cell death. Metacaspases are not biochemical, but sequence and functional homologes of caspases, as deletion of them rescues entirely different death scenarios. In this review we will summarize the current knowledge in S. cerevisiae on apoptotic processes, induced by internal and external triggers, which are dependent on the metacaspase gene YCA1. (C) 2008 Elsevier B.V. All rights reserved
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