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Plant Physiology：拟南芥PHB3作用于基因组完整性和根分生组织中的细胞增殖

已有 3571 次阅读 2019-1-26 08:11 |个人分类:每日摘要|系统分类:论文交流

Nuclear PROHIBITIN3 maintains genome integrity and cell proliferation in root meristem through MINICHROMOSOME MAINTENANCE 2

First author: Ruihua Huang; Affiliations: South China Normal University (华南师范大学): Guangzhou, China

Corresponding author: Shengchun Zhang

The nucleo-mitochondrial dual-localized proteins can act as gene expression regulators; however, few instances if these proteins have been described in plants. 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 CDKA1. 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 co-regulator 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 co-regulator that suppresses MCM2 expression to sustain genome integrity and cell proliferation for stem cell niche maintenance in Arabidopsis.

核-线粒体双元定位蛋白可以发挥调控基因表达的功能，然而，有关这些蛋白的报道在植物中的报道还很少。拟南芥PHB3参与植物的胁迫响应和发育进程，但其分子层面的机制还不清楚。本文中，作者报道了定位于核-线粒体的PHB3在调控基因组完整性和细胞增殖方面发挥重要的作用。PHB3受到DNA损伤试剂的诱导上调表达，并且胁迫诱导的PHB3蛋白在核中积累。PHB3的功能缺失突变体导致DNA损伤和根干细胞龛维持的缺陷。随后，干细胞调控子的表达模式被改变，且表达水平也有所下降。另外，phb3突变体的细胞分裂异常，细胞周期相关基因CycB1和CDKA1等的表达量也发生变化。此外，微染色体维持基因MCM2-MCM27在phb3突变体中的表达上调。MCM2表达水平的下调能够完全拯救phb3突变体的DNA损伤表型，并且能够部分恢复phb3突变体实生苗细胞增殖和根缺陷方面的缺陷。PHB3作为转录共调控子竞争性的结合到E2F的启动子上以抑制MCM2的表达，其中，E2F是顺式作用元件，与E2Fa一起调控主根的生长。综上，本文的研究发现定位于核的PHB3作为转录共调控因子抑制MCM2的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龛的维持。