Novel Factor Highly Conserved among Eukaryotes Controls Sexual Development in Fission Yeast

When starved for nutrient, the fission yeast Schizosaccharomyces pombe arrests in G1, but if mating partners are available, it resumes sexual development. The cells that have committed to sexual development subsequently perform conjugation, meiosis, and sporulation. The commitment to this alternative pathway requires the action of the Ste11 transcriptional factor. This factor is essential for the activation of many genes needed for the initiation and progression of conjugation and meiosis. Among them are mating-type genes, ste genes (including ste11+), mei2+, and rep1+ (11, 19, 24, 33, 34, 38, 40). Therefore, it is conceivable that the ste11+ gene and its product serve as key targets for the regulation of the onset of sexual development. Nitrogen starvation and carbon starvation are two major nutrient exhaustion signals that trigger sexual development. The cyclic AMP (cAMP)-Pka1 pathway mediates mostly a carbon source signal and partly a nitrogen source signal and negatively regulates ste11+ expression (2, 10, 15, 16, 33). The pac2+ gene, whose physiological role is unknown, also represses ste11+ expression (20). In addition, a stress signal transduced by the Wis1-Phh1/Sty1/Spc1 mitogen-activated protein kinase kinase–mitogen-activated protein kinase cascade is essential for ste11+ induction in response to nutrient starvation (18), which is mediated by the Atf1/Gad7 transcriptional factor (17, 35). Despite extensive studies, little is understood about the specific factors and mechanisms responsible for nitrogen starvation-invoked ste11+ induction. In the regulation of sexual development, Pat1/Ran1 kinase plays a unique role (1, 13, 14). Its primary role is to block the onset of meiosis until conjugation takes place, by inactivating Mei2, a key factor triggering the onset and progression of meiosis (39). The function of Ste11 protein itself is modulated by direct phosphorylation by Pat1 kinase, although its function in starting conjugation seems to be unchanged (22). Consequently, inactivation of Pat1 kinase in haploid cells unconditionally induces lethal meiosis, which can be suppressed by inactivation of the mei2+ gene. Since ste11+ is required for the expression of mei2+ (33), any factors that inhibit ste11+ expression or its function would rescue the pat1 lethality. Based on this assumption, we recently screened a gene library for multicopy suppressors of the pat1 lethality and isolated a new gene, named rcd1+, that is required for ste11+ expression specifically induced by nitrogen starvation. Strikingly, genes highly homologous to rcd1+ are present in many eukaryotes including humans. In this communication, we report the structure and function of this new gene and discuss the possibility of the presence of a highly conserved differentiation control mechanism throughout the eukaryotes.