Nuclear Prohibitin3 Maintains Genome Integrity and Cell Proliferation in the Root Meristem through Minichromosome Maintenance 2
Nuclear Prohibitin3 Maintains Genome Integrity and Cell Proliferation in the Root Meristem through Minichromosome Maintenance 2
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核 PROHIBITIN3 通过微型染色体维护维持根分生组织中的基因组完整性和细胞增殖 2
DOI：
10.1104/pp.18.01463
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发表时间：
2019-04-01
期刊：
影响因子：
7.4
通讯作者：
Zhang, Shengchun
中科院分区：
文献类型：
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作者：
Huang, Ruihua;Shu, Si;Zhang, Shengchun
核-线粒体双定位蛋白可作为基因表达调节因子，然而，这些蛋白在植物中的实例很少被描述。拟南芥（Arabidopsis thaliana）抑制蛋白3（PHB3）参与胁迫反应和发育过程，但尚不清楚这些作用如何在细胞核中在分子水平上实现。在这项研究中，我们表明，核线粒体PHB3在调节基因组稳定性和细胞增殖中起着至关重要的作用。PHB3被DNA损伤剂上调，并且应激诱导的PHB3蛋白在细胞核中积累。PHB3功能的丧失会导致DNA损伤和根干细胞生态位的维持缺陷。随后，根干细胞调节因子的表达模式和水平分别发生改变和下调。此外，phb3突变体显示异常的细胞分裂和细胞周期相关基因的表达改变，如CycB1和细胞周期蛋白依赖性激酶1。此外，微小染色体维持（MCM）基因，例如MCM2、MCM3、MCM4、MCM5、MCM6和MCM7，在phb3突变体中上调。降低MCM2表达水平基本上恢复了phb3突变体中的DNA损伤，并部分挽救了phb3幼苗的改变的细胞增殖和根缺陷。PHB3作为转录辅助调节因子，通过与E2Fa竞争性结合启动子E2F顺式作用元件来抑制MCM2的表达，从而调节初生根的生长。总的来说，这些研究结果表明，位于核内的PHB 3作为转录辅调节因子，抑制MCM2表达，以维持基因组完整性和细胞增殖，从而维持拟南芥干细胞生态位。
The nucleo-mitochondrial dual-localized proteins can act as gene expression regulators; however, few instances of these proteins have been described in plants. Arabidopsis (Arabidopsis thaliana) PROHIBITIN 3 (PHB3) is involved in stress responses and developmental processes, but it is unknown how these roles are achieved at the molecular level in the nucleus. In this study, we show that nucleo-mitochondrial PHB3 plays an essential role in regulating genome stability and cell proliferation. PHB3 is up-regulated by DNA damage agents, and the stress-induced PHB3 proteins accumulate in the nucleus. Loss of function of PHB3 results in DNA damage and defective maintenance of the root stem cell niche. Subsequently, the expression patterns and levels of the root stem cell regulators are altered and down-regulated, respectively. In addition, the phb3 mutant shows aberrant cell division and altered expression of cell cycle-related genes, such as CycB1 and Cyclin dependent kinase 1. Moreover, the minichromosome maintenance (MCM) genes, e.g. MCM2, MCM3, MCM4, MCM5, MCM6, and MCM7, are up-regulated in the phb3 mutant. Reducing the MCM2 expression level substantially recovers the DNA damage in the phb3 mutant and partially rescues the altered cell proliferation and root deficiency of phb3 seedlings. PHB3 acts as a transcriptional coregulator that represses MCM2 expression by competitively binding to the promoter E2F-cis-acting elements with E2Fa so as to modulate primary root growth. Collectively, these findings indicate that nuclear-localized PHB3 acts as a transcriptional coregulator that suppresses MCM2 expression to sustain genome integrity and cell proliferation for stem cell niche maintenance in Arabidopsis.