MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life.

David Guttery, Abhinay Ramaprasad, David J P Ferguson, Mohammad Zeeshan, Rajan Pandey, Declan Brady, Anthony A Holder, Arnab Pain, Rita Tewari

Research output: Contribution to journalArticlepeer-review

Abstract

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 $\textit{Plasmodium}$. Here, we present a functional, ultrastructural and transcriptomic analysis of $\textit{Plasmodium}$ parasites lacking MRE11 during its life cycle in both mammalian and mosquito vector hosts. Genetic disruption of $\textit{Plasmodium berghei mre11}$ (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 $\textit{Plasmodium}$ development during the mosquito stages and offers a potential target for therapeutic intervention during malaria parasite transmission.
Original languageEnglish (US)
Pages (from-to)2590
JournalCells
Volume9
Issue number12
DOIs
StatePublished - Dec 8 2020

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