MRE11 is crucial for malaria transmission and its absence affects expression of interconnected networks of key genes essential for life

MRE11 is crucial for malaria transmission and its absence affects expression of interconnected networks of key genes essential for life
复制标题

MRE11 对于疟疾传播至关重要,它的缺失会影响生命必需的关键基因互连网络的表达

DOI:
10.1101/2020.08.24.258657
复制
发表时间:
2020
期刊:
--
影响因子:
--
通讯作者:
Guttery D
Guttery D
中科院分区:
--
文献类型:
--
作者:
Guttery D

文献摘要

参考文献

相似文献

MeioticRecombination 11蛋白(MRE 11)在DNA损伤反应和维持基因组稳定性方面发挥着关键作用。然而,很少有人知道它的功能,在发展过程中的疟疾寄生虫疟原虫。在这里,我们提出了一个功能,超微结构和转录组分析ofPlasmodiumMRE 11在其生命周期中的哺乳动物和蚊子载体宿主。伯氏疟原虫mre 11(PbMRE 11)的遗传破坏导致与胞质和核变性相关的蚊中肠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。总的来说,我们的研究提供了一个全面的功能分析MRE 11的作用在疟原虫发育过程中的蚊子阶段,并提供了一个潜在的目标,在疟疾寄生虫传播的治疗干预。
TheMeioticRecombination 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 parasitePlasmodium. Here, we present a functional, ultrastructural and transcriptomic analysis ofPlasmodiumMRE11 during its life-cycle in both mammalian and mosquito vector hosts. Genetic disruption ofPlasmodium 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-sulphur cluster assembly. Overall, our study provides a comprehensive functional analysis of MRE11’s role inPlasmodiumdevelopment during the mosquito stages and offers a potential target for therapeutic intervention during malaria parasite transmission.
DOI: 10.1371/journal.ppat.1001242
发表时间: 2010-12-23
期刊: PLoS pathogens
影响因子: 6.7
作者:
Kehr S;Sturm N;Rahlfs S;Przyborski JM;Becker K
通讯作者: Becker K
DOI: 10.1126/science.1219723
发表时间: 2012-07-13
期刊: Science (New York, N.Y.)
影响因子: --
作者:
Stehling O;Vashisht AA;Mascarenhas J;Jonsson ZO;Sharma T;Netz DJ;Pierik AJ;Wohlschlegel JA;Lill R
通讯作者: Lill R
DOI: 10.1016/j.celrep.2013.01.032
发表时间: 2013-03-28
期刊: Cell reports
影响因子: 8.8
作者:
Patzewitz EM;Guttery DS;Poulin B;Ramakrishnan C;Ferguson DJ;Wall RJ;Brady D;Holder AA;Szöőr B;Tewari R
通讯作者: Tewari R
原因和后果
DOI: 10.1126/stke.2001.78.tw9
发表时间: 2001
期刊: Science's STKE
影响因子: --
作者:
Lin Zhang;Gargey Yagnik;Yong Peng;Jianxiu Wang;H. H. Xu;Yuanqiang Hao;You;F. Zhou
通讯作者: F. Zhou
DOI: 10.1016/j.molcel.2010.09.019
发表时间: 2010-10-22
期刊: Molecular cell
影响因子: 16
作者:
Ciccia A;Elledge SJ
通讯作者: Elledge SJ