MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life
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 <i>Plasmodium</i>. Here, we present a functional, ultrastructural and transcrip...
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MDPI AG
2020-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/12/2590 |
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| author | David S. Guttery Abhinay Ramaprasad David J. P. Ferguson Mohammad Zeeshan Rajan Pandey Declan Brady Anthony A. Holder Arnab Pain Rita Tewari |
| author_facet | David S. Guttery Abhinay Ramaprasad David J. P. Ferguson Mohammad Zeeshan Rajan Pandey Declan Brady Anthony A. Holder Arnab Pain Rita Tewari |
| author_sort | David S. Guttery |
| collection | DOAJ |
| description | 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 <i>Plasmodium</i>. Here, we present a functional, ultrastructural and transcriptomic analysis of <i>Plasmodium</i> parasites lacking MRE11 during its life cycle in both mammalian and mosquito vector hosts. Genetic disruption of <i>Plasmodium berghei mre11</i> (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 <i>Plasmodium</i> development during the mosquito stages and offers a potential target for therapeutic intervention during malaria parasite transmission. |
| first_indexed | 2024-03-10T14:20:05Z |
| format | Article |
| id | doaj.art-1311cbb1d3b6487baf891fba1dcd5837 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T14:20:05Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-1311cbb1d3b6487baf891fba1dcd58372023-11-20T23:25:48ZengMDPI AGCells2073-44092020-12-01912259010.3390/cells9122590MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for LifeDavid S. Guttery0Abhinay Ramaprasad1David J. P. Ferguson2Mohammad Zeeshan3Rajan Pandey4Declan Brady5Anthony A. Holder6Arnab Pain7Rita Tewari8Queens Medical Centre, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UKBiological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology, Thuwal 23955, Saudi ArabiaNuffield Department of Clinical Laboratory Science, University of Oxford, John Radcliffe Hospital, Oxford OX1 2JD, UKQueens Medical Centre, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UKQueens Medical Centre, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UKQueens Medical Centre, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UKThe Francis Crick Institute, London NW1 1AT, UKBiological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology, Thuwal 23955, Saudi ArabiaQueens Medical Centre, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UKThe 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 <i>Plasmodium</i>. Here, we present a functional, ultrastructural and transcriptomic analysis of <i>Plasmodium</i> parasites lacking MRE11 during its life cycle in both mammalian and mosquito vector hosts. Genetic disruption of <i>Plasmodium berghei mre11</i> (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 <i>Plasmodium</i> development during the mosquito stages and offers a potential target for therapeutic intervention during malaria parasite transmission.https://www.mdpi.com/2073-4409/9/12/2590<i>Plasmodium</i>DNA repairMRE11malariaribogenesis |
| spellingShingle | David S. Guttery Abhinay Ramaprasad David J. P. Ferguson Mohammad Zeeshan Rajan Pandey Declan Brady Anthony A. Holder Arnab Pain Rita Tewari MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life Cells <i>Plasmodium</i> DNA repair MRE11 malaria ribogenesis |
| title | MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life |
| title_full | MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life |
| title_fullStr | MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life |
| title_full_unstemmed | MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life |
| title_short | MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life |
| title_sort | mre11 is crucial for malaria parasite transmission and its absence affects expression of interconnected networks of key genes essential for life |
| topic | <i>Plasmodium</i> DNA repair MRE11 malaria ribogenesis |
| url | https://www.mdpi.com/2073-4409/9/12/2590 |
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