Cohesion promotes nucleolar structure and function.
Cohesion promotes nucleolar structure and function.
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凝聚力促进核仁结构和功能。
DOI：
10.1091/mbc.e13-07-0377
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发表时间：
2014-02
影响因子：
3.3
通讯作者：
Gerton JL
中科院分区：
文献类型：
--
作者：
Harris B;Bose T;Lee KK;Wang F;Lu S;Ross RT;Zhang Y;French SL;Beyer AL;Slaughter BD;Unruh JR;Gerton JL
黏连蛋白乙酰转移酶 Eco1 或黏连蛋白环的突变会损害芽殖酵母的核仁功能。 Eco1 中与人类疾病罗伯茨综合征相关的突变会损害核糖体 DNA 和转录的循环相互作用。单个细胞周期中内聚力的耗尽会破坏核仁的完整性。尽管所涉及的分子机制尚不清楚，但粘连蛋白复合物有助于核糖体功能。粘连蛋白功能受损与一类称为粘连蛋白病的疾病有关。当突变减少粘连蛋白 Smc3 亚基的乙酰化时，就会发生一种粘连病，罗伯茨综合征 (RBS)。粘连蛋白乙酰转移酶的突变与酵母和人类细胞中 rRNA 产生、核糖体生物合成和蛋白质合成受损有关。从细菌到人类细胞，粘连蛋白与核糖体 DNA (rDNA) 的结合在进化上是保守的。我们报告酵母中的 RBS 突变 (eco1-W216G) 表现出核仁紊乱和 rDNA 环减少。 RNA 聚合酶 I 对基因的占用保持正常，表明募集并未受损。 RBS 突变体中 rRNA 产生受损与 rRNA 裂解速度减慢同时发生。除了 RBS 突变之外，粘连蛋白环任何亚基的突变都与核糖体生物发生的缺陷有关。单个细胞周期中内聚力的耗尽或人为破坏与核仁完整性的丧失相关，这表明 rDNA 的缺陷可直接归因于内聚力的丧失。我们的结果强烈表明，内聚力提供的 rDNA 组织对于核仁的形成和功能至关重要。
Mutations in the cohesin acetyltransferase Eco1 or the cohesin ring compromise nucleolar function in budding yeast. A mutation in Eco1 that is associated with the human disease Roberts syndrome compromises looping interactions at the ribosomal DNA and transcription. Depletion of cohesion in a single cell cycle disrupts nucleolar integrity. The cohesin complex contributes to ribosome function, although the molecular mechanisms involved are unclear. Compromised cohesin function is associated with a class of diseases known as cohesinopathies. One cohesinopathy, Roberts syndrome (RBS), occurs when a mutation reduces acetylation of the cohesin Smc3 subunit. Mutation of the cohesin acetyltransferase is associated with impaired rRNA production, ribosome biogenesis, and protein synthesis in yeast and human cells. Cohesin binding to the ribosomal DNA (rDNA) is evolutionarily conserved from bacteria to human cells. We report that the RBS mutation in yeast (eco1-W216G) exhibits a disorganized nucleolus and reduced looping at the rDNA. RNA polymerase I occupancy of the genes remains normal, suggesting that recruitment is not impaired. Impaired rRNA production in the RBS mutant coincides with slower rRNA cleavage. In addition to the RBS mutation, mutations in any subunit of the cohesin ring are associated with defects in ribosome biogenesis. Depletion or artificial destruction of cohesion in a single cell cycle is associated with loss of nucleolar integrity, demonstrating that the defects at the rDNA can be directly attributed to loss of cohesion. Our results strongly suggest that organization of the rDNA provided by cohesion is critical for formation and function of the nucleolus.