MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life.
MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life.
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DOI：
10.3390/cells9122590
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发表时间：
2020-12-03
期刊：
影响因子：
6
通讯作者：
Tewari R
中科院分区：
文献类型：
--
作者：
Guttery DS;Ramaprasad A;Ferguson DJP;Zeeshan M;Pandey R;Brady D;Holder AA;Pain A;Tewari R
减数分裂重组11蛋白（MRE 11）在DNA损伤反应和维持基因组稳定性中起着关键作用。然而，很少有人知道它在疟疾寄生虫疟原虫发育过程中的功能。在这里，我们对哺乳动物和蚊子载体宿主中缺乏MRE 11的疟原虫寄生虫在其生命周期中的功能、超微结构和转录组学分析。伯氏疟原虫mre 11（PbMRE 11）的遗传破坏导致与细胞质和核变性相关的蚊子中肠中卵囊发育的显著延迟，沿着孢子生殖的消融和随后的寄生虫传播。此外，PbMRE 11的缺乏导致参与关键相互关联的生物过程的基因的显著转录下调，这些生物过程对所有真核生物都是至关重要的，包括核糖核蛋白生物发生、剪接体功能和铁硫簇组装。总之，我们的研究提供了一个全面的功能分析MRE 11在疟原虫发育过程中的蚊子阶段的作用，并提供了一个潜在的治疗干预疟疾寄生虫传播的目标。
The meiotic recombination 11 protein (MRE11) plays a key role in DNA damage response and maintenance of genome stability. However, little is known about its function during development of the malaria parasite Plasmodium. Here, we present a functional, ultrastructural and transcriptomic analysis of Plasmodium parasites lacking MRE11 during its life cycle in both mammalian and mosquito vector hosts. Genetic disruption of Plasmodium berghei mre11 (PbMRE11) results in significant retardation of oocyst development in the mosquito midgut associated with cytoplasmic and nuclear degeneration, along with concomitant ablation of sporogony and subsequent parasite transmission. Further, absence of PbMRE11 results in significant transcriptional downregulation of genes involved in key interconnected biological processes that are fundamental to all eukaryotic life including ribonucleoprotein biogenesis, spliceosome function and iron–sulfur cluster assembly. Overall, our study provides a comprehensive functional analysis of MRE11′s role in Plasmodium development during the mosquito stages and offers a potential target for therapeutic intervention during malaria parasite transmission.
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影响因子：
6.7
作者：
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通讯作者：
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