Meiosis generates haploid gametes from diploid cells and is an almost universal feature of eukaryotic organisms. But little is known about how the switch from mitotic to meiotic cell cycles is molecularly controlled. In the fission yeast Schizosaccharomyces pombe, inactivation of the protein kinase Pat1(Ran1) upon nutrient deprivation triggers entry into the meiotic cell cycle. Here we show that the RNA-binding protein Mei2 is a substrate of Pat1 kinase and that dephosphorylation of Mei2 is sufficient to switch cells from the mitotic cell cycle into meiosis. Mei2 is localized mainly in the cytoplasm of proliferating cells but is seen as a single spot close to the microtubule organizing centre in prophase nuclei during meiosis. Our results, and others from a metazoan, emphasize the crucial role of RNA-binding proteins in the initiation and execution of meiosis.

In fission yeast, the onset of meiosis is triggered by activation of the RNA-binding protein Mei2p. We screened for a high-copy-number suppressor of the ectopic meiosis induced by expression of an active form of Mei2p. Consequently we isolated a truncated form of a novel gene, named mip1, from a fission yeast genomic library. The mip1 gene encoded a protein of 1,313 amino acids which carried a WD-repeat motif in the C-terminal region and was apparently conserved among eukaryotes. Mip1p was cytoplasmic, and two-hybrid and immunoprecipitation analyses demonstrated that Mip1p was bound to Mei2p in vivo. Genetic evidence indicated that wild-type Mip1p was required for the function of Mei2p to induce meiosis and that the truncated form of it (Mip1-15p) dominantly interfered with Mei2p. Mip1p appeared to be involved also in conjugation, associating with Ste11p, which is a key transcription factor for sexual development. Furthermore, Mip1p was essential for cell growth, to which neither Mei2p nor Ste11p is relevant. These results suggest that Mip1p assists functional expression of a number of proteins required for proliferation and sexual development in fission yeast.Sexual differentiation in the fission yeast Schizosaccharomyces pombe proceeds under nutrient starvation (4, 27, 28). Ste11p, which is a high-mobility-group protein, serves as a key transcription factor in this process. Upon starvation, Ste11p activates a number of genes required for mating and/or meiosis, including the mating-type genes (mat1-P and mat1-M) and mei2 (21). The mei2 gene encodes a pivotal regulator of meiosis (3,20,25). Pat1p (Ran1p) kinase (6,11,17), which is active during the mitotic cell cycle, phosphorylates Mei2p on two amino acid residues, Ser438 and Thr527, and thereby blocks the function of Mei2p (24). In diploid cells, the gene products of mat1-P and mat1-M cooperate to turn on expression of mei3, which encodes an inhibitor of Pat1p kinase and hence induces derepression of Mei2p (12,13,24,26). Thus, mei2 is activated both transcriptionally and posttranscriptionally in diploid cells under starved conditions. If a mutant Mei2p carrying alanine residues in place of Ser438 and Thr527 (Mei2-SATA) is expressed in proliferating cells, the cells cease growth immediately and enter meiosis, indicating that dephosphorylated Mei2p has the ability to switch the mitotic cell cycle to the meiotic one (24).Mei2p is an RNA-binding protein with three RNA recognition motifs that is required for both induction of premeiotic DNA synthesis and promotion of the first meiotic division (meiosis I). Cytoplasmic Mei2p performs the former function, and the RNA-binding ability of Mei2p is essential for it. To perform the latter function, Mei2p must move into the nucleus, where it forms a distinct dot structure. A specific RNA species, named meiRNA, has been shown to promote meiosis I as a cofactor that assists nuclear transport of Mei2p (25,29). However, the molecular function of Mei2p in the cytoplasm as well as that in the nucleus remains unknown.To identify ...

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