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

Agarwala SD, Blitzblau HG, Hochwagen A, Fink GR - PLoS Genet. (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Whitehead Institute, Cambridge, Massachusetts, USA.

ABSTRACT
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.

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IME1 and IME2 are necessary for RTG PH development.A) Representative bud morphology after RTG3 in wild-type (SAy821), ime1Δ/Δ (SAy834) and ime2Δ/Δ (SAy859). Arrows indicate primary buds. The same strains were photographed after growth on SLAD for 6 days (bottom panels). B) Axial ratio quantification of RTG3 cells for strains in (A) (n = 200 cells/strain).
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pgen-1002732-g002: IME1 and IME2 are necessary for RTG PH development.A) Representative bud morphology after RTG3 in wild-type (SAy821), ime1Δ/Δ (SAy834) and ime2Δ/Δ (SAy859). Arrows indicate primary buds. The same strains were photographed after growth on SLAD for 6 days (bottom panels). B) Axial ratio quantification of RTG3 cells for strains in (A) (n = 200 cells/strain).

Mentions: To probe the genetic underpinnings of RTG-PH development, we investigated the roles of factors known to regulate both meiosis and PH growth. The transcription factor Ime1 is essential for entry into the meiotic program [5]. Similarly, loss of the meiosis-specific CDK-like kinase Ime2 leads to an extreme delay in meiotic entry [28]. Both factors are also required for PH development on SLAD medium [5], [6], [7]. We found that in the absence of either IME1 or IME2, cells failed to enter RTG-PH development and instead formed ovoid buds upon RTG3 (Figure 2A, 2B), although it should be noted that ime2Δ/Δ cells were able to form elongated RTG-PH buds after extended periods in SPO (Figure S3). These data suggest that, upon severe starvation, Ime1 and Ime2 promote both RTG-PH development and meiosis.


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

Agarwala SD, Blitzblau HG, Hochwagen A, Fink GR - PLoS Genet. (2012)

IME1 and IME2 are necessary for RTG PH development.A) Representative bud morphology after RTG3 in wild-type (SAy821), ime1Δ/Δ (SAy834) and ime2Δ/Δ (SAy859). Arrows indicate primary buds. The same strains were photographed after growth on SLAD for 6 days (bottom panels). B) Axial ratio quantification of RTG3 cells for strains in (A) (n = 200 cells/strain).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369947&req=5

pgen-1002732-g002: IME1 and IME2 are necessary for RTG PH development.A) Representative bud morphology after RTG3 in wild-type (SAy821), ime1Δ/Δ (SAy834) and ime2Δ/Δ (SAy859). Arrows indicate primary buds. The same strains were photographed after growth on SLAD for 6 days (bottom panels). B) Axial ratio quantification of RTG3 cells for strains in (A) (n = 200 cells/strain).
Mentions: To probe the genetic underpinnings of RTG-PH development, we investigated the roles of factors known to regulate both meiosis and PH growth. The transcription factor Ime1 is essential for entry into the meiotic program [5]. Similarly, loss of the meiosis-specific CDK-like kinase Ime2 leads to an extreme delay in meiotic entry [28]. Both factors are also required for PH development on SLAD medium [5], [6], [7]. We found that in the absence of either IME1 or IME2, cells failed to enter RTG-PH development and instead formed ovoid buds upon RTG3 (Figure 2A, 2B), although it should be noted that ime2Δ/Δ cells were able to form elongated RTG-PH buds after extended periods in SPO (Figure S3). These data suggest that, upon severe starvation, Ime1 and Ime2 promote both RTG-PH development and meiosis.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Whitehead Institute, Cambridge, Massachusetts, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus