MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life.
David S GutteryAbhinay RamaprasadDavid J P FergusonMohammad ZeeshanRajan PandeyDeclan BradyAnthony A HolderArnab PainRita TewariPublished in: Cells (2020)
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.
Keyphrases
- plasmodium falciparum
- aedes aegypti
- dna damage response
- genome wide
- life cycle
- randomized controlled trial
- dengue virus
- poor prognosis
- dna repair
- signaling pathway
- dna damage
- gene expression
- transcription factor
- oxidative stress
- small molecule
- copy number
- binding protein
- cell proliferation
- single cell
- risk assessment
- climate change
- rna seq
- protein protein