RNA methylation by the MIS complex regulates a cell fate decision in yeast

• Published in: PLoS genetics Vol. 8; no. 6; p. e1002732
• Main Authors: Agarwala, Sudeep D, Blitzblau, Hannah G, Hochwagen, Andreas, Fink, Gerald R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.06.2012; Public Library of Science (PLoS)
• Subjects: Biology; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Differentiation - genetics; Cell division; Cell fate; Cloning; Defects; Differentiation; Diploids; DNA methylation; Experiments; Fungal Proteins - genetics; Fungal Proteins - metabolism; Genetic aspects; Hyphae - genetics; Hyphae - growth & development; Meiosis; Meiosis - genetics; Methylation; Methyltransferase; Microbial genetics; mRNA; Nutrient availability; Nutrients; Nutritional Physiological Phenomena - genetics; Nutritional Physiological Phenomena - physiology; Physiological aspects; Post-transcription; Prophase; Proteins; RNA; RNA modification; RNA, Messenger - genetics; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Signal Transduction - genetics; Spores; Spores, Fungal - genetics; Spores, Fungal - metabolism; Sporulation; Starvation; tRNA Methyltransferases - genetics; tRNA Methyltransferases - metabolism; Yeast; Yeast fungi; United States
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1002732

For the yeast Saccharomyces cerevisiae, nutrient limitation is a key developmental signal causing diploid cells to switch from yeast-form budding to either foraging pseudohyphal (PH) growth or meiosis and sporulation. Prolonged starvation leads to lineage restriction, such that cells exiting meiotic prophase are committed to complete sporulation even if nutrients are restored. Here, we have identified an earlier commitment point in the starvation program. After this point, cells, returned to nutrient-rich medium, entered a form of synchronous PH development that was morphologically and genetically indistinguishable from starvation-induced PH growth. We show that lineage restriction during this time was, in part, dependent on the mRNA methyltransferase activity of Ime4, which played separable roles in meiotic induction and suppression of the PH program. Normal levels of meiotic mRNA methylation required the catalytic domain of Ime4, as well as two meiotic proteins, Mum2 and Slz1, which interacted and co-immunoprecipitated with Ime4. This MIS complex (Mum2, Ime4, and Slz1) functioned in both starvation pathways. Together, our results support the notion that the yeast starvation response is an extended process that progressively restricts cell fate and reveal a broad role of post-transcriptional RNA methylation in these decisions.