Queens Medical Centre, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK.
Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology, Thuwal 23955, Saudi Arabia.
Cells. 2020 Dec 3;9(12):2590. doi: 10.3390/cells9122590.
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 . Here, we present a functional, ultrastructural and transcriptomic analysis of parasites lacking MRE11 during its life cycle in both mammalian and mosquito vector hosts. Genetic disruption of (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 development during the mosquito stages and offers a potential target for therapeutic intervention during malaria parasite transmission.
减数分裂重组蛋白 11（MRE11）在 DNA 损伤反应和维持基因组稳定性中发挥着关键作用。然而，人们对其在疟原虫发育过程中的功能知之甚少。在这里，我们对疟原虫生命周期中缺乏 MRE11 的寄生虫进行了功能、超微结构和转录组分析，这些寄生虫在哺乳动物和蚊子媒介宿主中都缺乏 MRE11。（PbMRE11）的基因缺失导致蚊子中肠卵囊发育显著滞后，与细胞质和核退化有关，同时伴随着孢子生殖和随后寄生虫传播的消融。此外，PbMRE11 的缺失导致涉及关键相互关联的生物过程的基因转录显著下调，这些过程对于所有真核生物的生命都是基本的，包括核糖核蛋白生物发生、剪接体功能和铁硫簇组装。总的来说，我们的研究提供了 MRE11 在蚊子阶段疟原虫发育中的作用的全面功能分析，并为疟疾寄生虫传播期间的治疗干预提供了一个潜在的靶点。
