MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life.
Type
ArticleAuthors
Guttery, David
Ramaprasad, Abhinay

Ferguson, David J P

Zeeshan, Mohammad
Pandey, Rajan
Brady, Declan

Holder, Anthony A
Pain, Arnab

Tewari, Rita
KAUST Department
Bioscience ProgramBiological and Environmental Sciences and Engineering (BESE) Division
Date
2020-12-08Submitted Date
2020-11-03Permanent link to this record
http://hdl.handle.net/10754/664833
Metadata
Show full item recordAbstract
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.Citation
Guttery, D. S., Ramaprasad, A., Ferguson, D. J. P., Zeeshan, M., Pandey, R., Brady, D., … Tewari, R. (2020). MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life. Cells, 9(12), 2590. doi:10.3390/cells9122590Sponsors
We thank Julie Rogers for technical assistance and the personnel at the Bioscience Core Laboratory (BCL) in KAUST for sequencing the RNA samples and producing the raw datasets.This project was funded by MRC Investigator Award and MRC project grants to R.T. [G0900109, G0900278, MR/K011782/1] and also supported by a faculty baseline funding [BAS/1/1020-01-01] to A.P., A.A.H. is supported by the Francis Crick Institute (FC010097) which receives its core funding from Cancer Research UK (FC010097), the UK Medical Research Council (FC010097) and the Wellcome Trust (FC010097). A.P. and A.R. are funded by KAUST. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
Publisher
MDPI AGJournal
CellsPubMed ID
33287434Additional Links
https://www.mdpi.com/2073-4409/9/12/2590ae974a485f413a2113503eed53cd6c53
10.3390/cells9122590
Scopus Count
Except where otherwise noted, this item's license is described as This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
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