Molecular Mechanisms for the Regulation of Meiosis

1.筛选了分裂酵母减数分裂相关基因mei4、sp5、ssm4等基因，筛选了减数分裂过程中必需的meiRNA缺失突变体。结果表明，这种抑制不是由它们的蛋白质产物引起的，而是由它们的部分mRNAs引起的。有趣的是，这些mRNA是不稳定的，即使人工表达，也不会在有丝分裂生长的细胞中积累，而且导致这种不稳定的区域与抑制meiRNA丢失的区域重叠。因此，我们推测，这些mRNAs携带一个区域，使它们在有丝分裂细胞周期中不稳定，并在减数分裂期间运行某种机制来稳定它们。2.裂殖酵母Mei2p是减数分裂启动的调控因子，在前期I期细胞核内形成点状结构。我们已经证明这个点是Mei2p和新生的meiRNA的复合体，刚刚从基因转录而来。3.我们分离到一个新的裂解酵母Tor1突变体，它编码有性发育所需的TOR激酶。然后，我们分离出编码AGC家族的一种激酶的gad8，作为该突变体的抑制因子。分析表明，Tor1p通过Gad8p调节性发育和应激反应。4.我们分离到了线虫DAZ-1，它是导致哺乳动物无精子症的DAZ的同源物。在DAZ-1基因缺陷的虫体中，减数分裂过程在卵子发生过程中停止在粗线期。即使在性腺增殖期的生殖细胞中，它们也显示出异常的核形态。DAZ-1基因缺陷的虫子在减数分裂阶段没有表现出核仁的扩张和中央细胞质核心的形成，这些细胞在蛋白质合成方面似乎不那么活跃。其他数据表明，DAZ-1可能也参与了性腺的性别转换。

1.We screened for suppressors of the fission yeast meiosis-defective mutant lacking meiRNA, which is indispensable for meiosis I, and isolated meiosis-specific genes mei4, spo5, ssm4 and others. It turned out that the suppression was caused not by their protein products but by part of their mRNAs. Interestingly, these mRNAs were unstable and did not accumulate in mitotically growing cells, even if artificially expressed, and the region responsible for this instability overlapped with the region that suppressed loss of meiRNA. Thus we speculate that these mRNAs carry a region that renders them unstable in the mitotic cell cycle, and that a certain mechanism operates to stabilize them during meiosis. 2.Fission yeast Mei2p, the regulator of the initiation of meiosis, forms a dot structure in prophase I nuclei. We have demonstrated that this dot is a complex of Mei2p and nascent meiRNA, just transcribed from the gene. 3.We isolate a new mutant of fission yeast tor1, which encodes a TOR kinase required for sexual development. We then isolated gad8, which encoded a kinase of the AGC family, as a suppressor of this mutant. Analysis has shown that Tor1p regulates sexual development and stress responses through Gad8p. 4.We isolated C. elegans DAZ-1, a homolog of DAZ responsible for azoospermia in mammals. In DAZ-1-defective worms, the meiotic process was arrested at pachytene during oogenesis. They showed abnormal nuclear morphology even in germ cells at the proliferative stage in the gonad. The DAZ-1-defective worms did not show expansion of nucleoli nor formation of the central cytoplasmic core in germ cells at the meiotic stage, and these cells appeared to be less active in protein synthesis. Other data have suggested that DAZ-1 may also be involved in switching sexuality of the gonad.