Molecular Mechanisms for the Regulation of Meiosis

减数分裂调节的分子机制

• 批准号: 11102002
• 负责人: YAMAMOTO Masayuki
• 金额: $ 206.66万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Specially Promoted Research
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11102002/
• 关键词: MEIOSIS; FISSION YEAST; WORM; MEIOTIC DIVISION; mRNA; STABILITY; TOR KINASE; NUCLEAR MORPHOLOGY; RNA結合タンパク質; プロテインフォスファターゼ; セントロメア; 精子形成; 転写因子; cAMP; プロテインキナーゼ; 14-3-3タンパク質; コヒーシン; 還元分裂; RNAi; 核移行; 14-3-3; 卵形成; 太糸期

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.

1.我们筛选了缺乏Meirna的裂变酵母菌缺陷突变体的抑制剂，这对于减数分裂I是必不可少的，并且分离出了减数分裂特异性基因MEI4，SPO5，SSM4等。事实证明，抑制不是由其蛋白质产品而是由其mRNA引起的。有趣的是，这些mRNA是不稳定的，即使人为地表达，也不会积聚在有丝分裂生长的细胞中，并且负责这种不稳定性的区域与抑制Meirna损失的区域重叠。因此，我们推测这些mRNA具有在有丝分裂细胞周期中使它们不稳定的区域，并且某种机制在减数分裂过程中稳定它们。 2.酵母菌摄入酵母菌的调节剂是减数分裂的调节剂，形成了先前I核中的点结构。我们已经证明了这个点是Mei2p和新生的Meirna的复杂，刚从该基因转录。 3.我们隔离了一个新的裂变酵母Tor1突变体，该突变体编码了性发育所需的TOR激酶。然后，我们隔离了编码AGC家族的激酶的GAD8，作为该突变体的抑制剂。分析表明，TOR1P通过GAD8P调节性发展和压力反应。 4.我们隔离了秀丽隐杆线虫DAZ-1，是DAZ的同源物，负责哺乳动物中的Azoospermia。在DAZ-1缺陷性蠕虫中，减数分裂过程在卵子发生过程中在Pachytene中被捕。他们即使在性腺增殖阶段的生殖细胞中也表现出异常的核形态。在减数分裂阶段，DAZ-1缺陷蠕虫没有显示出生殖细胞中核仁的膨胀或中央细胞质核的形成，这些细胞在蛋白质合成中似乎不太活跃。其他数据表明，DAZ-1也可能参与改变性腺的性行为。

项目成果

Yamamoto, M.: "Initiation of meiosis"In : The Molecular Biology of Schizosacchromyces pombe, (R.Egel, ed.), Springer-Verlag, Berlin. 297-309 (2003)

Yamamoto, M.：“减数分裂的起始”，见：粟酒裂殖酵母的分子生物学（R.Egel，编辑），Springer-Verlag，柏林。

Kitajima, T.: "Rec8 cleavage by separase is required for meiotic nuclear divisions in fission yeast."EMBO Journal. 22. 5643-5653 (2003)

Kitajima, T.：“裂殖酵母减数分裂核分裂需要分离酶对 Rec8 进行切割。”EMBO 杂志。

Kuromori,T.: "Members of the Arabidopsis 14-3-3 gene family trans-complement two types of defects in fission yeast."Plant Science. 158. 155-161 (2000)

Kuromori,T.：“拟南芥 14-3-3 基因家族的成员反式补充裂殖酵母中的两种类型的缺陷。”植物科学。

Shimada, T. et al.: "The fission yeast meiotic regulator Mei2p forms a dot structure in the horse-tail nucleus in association with the sme2 locus on chromosome II."Molecular Biology of the Cell. 14. 2461-2469 (2003)

Shimada, T. 等人：“裂殖酵母减数分裂调节因子 Mei2p 在马尾核中形成一个点结构，与 II 号染色体上的 sme2 基因座相关。”细胞的分子生物学。

Kitajima, T.: "The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis."Nature. 427. 510-517 (2004)

Kitajima, T.：“保守的动粒蛋白 shugoshin 在减数分裂过程中保护着丝粒的凝聚力。”《自然》。