Edwards-Smallbone, J, Jensen, A, Roberts, L, Totanes, FI, Hart, SR and Merrick, CJ (2022) Plasmodium falciparum GBP2 is a telomere-associated protein that binds to G-quadruplex DNA and RNA. Frontiers in Cellular and Infection Microbiology, 12. ISSN 2235-2988

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In the early-diverging protozoan parasite Plasmodium, few telomere-binding proteins have been identified and several are unique. Plasmodium telomeres, like those of most eukaryotes, contain guanine-rich repeats that can form G-quadruplex structures. In model systems, quadruplex-binding drugs can disrupt telomere maintenance and some quadruplex-binding drugs are potent anti-plasmodial agents. Therefore, telomere-interacting and quadruplex-interacting proteins may offer new targets for anti-malarial therapy. Here, we report that P. falciparum GBP2 is such a protein. It was identified via Proteomics of Isolated Chromatin fragments', applied here for the first time in Plasmodium. In vitro, PfGBP2 binds specifically to G-rich telomere repeats in quadruplex form and it can also bind to G-rich RNA. In vivo, PfGBP2 partially colocalises with the known telomeric protein HP1 but is also found in the cytoplasm, probably due to its affinity for RNA. Consistently, its interactome includes numerous RNA-associated proteins. PfGBP2 is evidently a multifunctional DNA/RNA-binding factor in Plasmodium.

Item Type: Article
Additional Information: © 2022 Edwards-Smallbone, Jensen, Roberts, Totañes, Hart and Merrick. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Uncontrolled Keywords: Plasmodium, malaria, G-quadruplex, telomere, proteomics of isolated chromatin fragments, GBP2
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > School of Pharmacy and Bioengineering
Depositing User: Symplectic
Date Deposited: 24 Mar 2022 09:45
Last Modified: 02 Mar 2023 11:03
URI: https://eprints.keele.ac.uk/id/eprint/10762

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