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Regulation of meiosis in fission yeast
1Department of Biophysics and Biochemistry, Graduate School of Science, University of Tokyo, Japan.
Abstract:
The fission yeast Schizosaccharomyces pombe initiates sexual development under starved conditions. Nutritional starvation decreases the level of intracellular cAMP. This decrease induces expression of the ste11 gene, which encodes a key transcription factor for genes required for mating and meiosis. Mutational analyses of S. pombe genes encoding components of the cAMP cascade have shown that S. pombe cells stay in the mitotic cell cycle as long as the level of cAMP-dependent protein kinase activity is high, but are committed to mating and meiosis if this activity is lowered. To initiate meiosis in S. pombe, a protein kinase encoded by pat1 (also called ran1) should be inactivated. This inactivation results from deprivation of nutrients via a cascade of expression of genes including ste11. The mei2 gene encodes a factor indispensable for the initiation of meiosis, and its expression is regulated directly by Ste11. If Pat1 kinase is intact, it blocks Mei2 function. Mei2 is required at two distinct stages of meiosis, once prior to premeiotic DNA synthesis and then prior to the first meiotic division (meiosis I). Mei2 is an RNA-binding protein, and forms a complex with a specific RNA species to promote meiosis I. This RNA species, named meiRNA, is polyadenylated but is unlikely to encode a protein product. It is essential for meiosis I, but not for either cell growth or premeiotic DNA synthesis. These observations unequivocally demonstrate that RNA plays a critical role in the control of meiosis.
Insights
Nutritional starvation in fission yeast triggers sexual development by lowering cAMP levels, activating mating and meiosis genes. A key RNA molecule, meiRNA, is essential for the meiotic process in Schizosaccharomyces pombe.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Fission yeast, Schizosaccharomyces pombe, undergoes sexual development under nutrient starvation.
- Nutritional stress reduces intracellular cyclic adenosine monophosphate (cAMP) levels, influencing cell cycle progression.
- The cAMP signaling pathway regulates the transition from mitotic cell cycle to mating and meiosis.
Purpose of the Study:
- To investigate the molecular mechanisms controlling sexual development and meiosis initiation in Schizosaccharomyces pombe.
- To elucidate the role of cAMP signaling and specific regulatory factors in meiotic commitment.
Main Methods:
- Mutational analyses of genes involved in the cAMP cascade.
- Gene expression studies focusing on ste11 and mei2.
- Biochemical characterization of Mei2 protein and its interaction with meiRNA.
Main Results:
- Decreased cAMP levels induce ste11 gene expression, a key transcription factor for mating and meiosis.
- Inactivation of Pat1 kinase (ran1) is necessary for meiosis initiation and is triggered by nutrient deprivation.
- Mei2, regulated by Ste11, is essential for meiosis and functions by forming a complex with a non-coding RNA, meiRNA, crucial for meiosis I.
Conclusions:
- The cAMP-dependent protein kinase activity level dictates cell cycle fate (mitosis vs. mating/meiosis).
- Nutrient starvation initiates a signaling cascade leading to Pat1 kinase inactivation and Mei2 activation.
- Non-coding RNA (meiRNA) plays a critical, essential role in regulating the control of meiosis I in fission yeast.