Project description:N6-methyladenosine (m6A) is the most ubiquitous mRNA base modification, but little is known about its precise location, temporal dynamics, and regulation. Here, we generated genomic maps of m6A sites in meiotic yeast transcripts at nearly single-nucleotide resolution, identifying 1,308 putatively methylated sites within 1,183 transcripts. We validated 8/8 methylation sites in different genes with direct genetic analysis, demonstrated that methylated sites are significantly conserved in a related species, and built a model that predicts methylated sites directly from sequence. Sites vary in their methylation profiles along a dense meiotic time-course, and are regulated both locally, via predictable methylatability of each site, and globally, through the core meiotic circuitry. The methyltransferase complex components localize to the yeast nucleolus, and this localization is essential for mRNA methylation. Our data illuminates a conserved, dynamically regulated methylation program in yeast meiosis, and provides an important resource for studying the function of this epitranscriptomic modification. Examination of m6A methylation under various conditions
Project description:N6-methyladenosine (m6A) is the most ubiquitous mRNA base modification, but little is known about its precise location, temporal dynamics, and regulation. Here, we generated genomic maps of m6A sites in meiotic yeast transcripts at nearly single-nucleotide resolution, identifying 1,308 putatively methylated sites within 1,183 transcripts. We validated 8/8 methylation sites in different genes with direct genetic analysis, demonstrated that methylated sites are significantly conserved in a related species, and built a model that predicts methylated sites directly from sequence. Sites vary in their methylation profiles along a dense meiotic time-course, and are regulated both locally, via predictable methylatability of each site, and globally, through the core meiotic circuitry. The methyltransferase complex components localize to the yeast nucleolus, and this localization is essential for mRNA methylation. Our data illuminates a conserved, dynamically regulated methylation program in yeast meiosis, and provides an important resource for studying the function of this epitranscriptomic modification.
Project description:Ray2013 - S.cerevisiae meiosis-specific metabolic network
Meiosis is a strongly concerved cell division program that generates haploid gametes from a diploid parental cell. Successful meiosis is the fundamental basis of sexual reproduction. Multiple lines of evidence suggest a tight link between meiosis and metabolism. Here, yeast meiosis is studied to elucidate the link between reproduction and metabolism. Network flux is obtained using GLPK (GNU Linear Programming Kit) supported by the COBRA Toolbox for Matlab.
This model is described in the article:
Characterization of the metabolic requirements in yeast meiosis.
Ray D, Ye P.
PLoS One. 2013 May 8;8(5):e63707.
Abstract:
The diploid yeast Saccharomyces cerevisiae undergoes mitosis in glucose-rich medium but enters meiosis in acetate sporulation medium. The transition from mitosis to meiosis involves a remarkable adaptation of the metabolic machinery to the changing environment to meet new energy and biosynthesis requirements. Biochemical studies indicate that five metabolic pathways are active at different stages of sporulation: glutamate formation, tricarboxylic acid cycle, glyoxylate cycle, gluconeogenesis, and glycogenolysis. A dynamic synthesis of macromolecules, including nucleotides, amino acids, and lipids, is also observed. However, the metabolic requirements of sporulating cells are poorly understood. In this study, we apply flux balance analyses to uncover optimal principles driving the operation of metabolic networks over the entire period of sporulation. A meiosis-specific metabolic network is constructed, and flux distribution is simulated using ten objective functions combined with time-course expression-based reaction constraints. By systematically evaluating the correlation between computational and experimental fluxes on pathways and macromolecule syntheses, the metabolic requirements of cells are determined: sporulation requires maximization of ATP production and macromolecule syntheses in the early phase followed by maximization of carbohydrate breakdown and minimization of ATP production in the middle and late stages. Our computational models are validated by in silico deletion of enzymes known to be essential for sporulation. Finally, the models are used to predict novel metabolic genes required for sporulation. This study indicates that yeast cells have distinct metabolic requirements at different phases of meiosis, which may reflect regulation that realizes the optimal outcome of sporulation. Our meiosis-specific network models provide a framework for an in-depth understanding of the roles of enzymes and reactions, and may open new avenues for engineering metabolic pathways to improve sporulation efficiency.
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Project description:This study newly identified Tripelennamine (TA) as an inhibitor of yeast meiosis and sporulation. To examine if and how exposure of sporulating yeast cells to TA changes the meiotic transcriptional program cells were sporulated for 0, 4, and 8 hours in the presence or absence of 100 uM TA.