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Plasmodium falciparum GBP2 is a telomere-associated protein that binds to G-quadruplex DNA and RNA

Edwards-Smallbone, James; L. Jensen, Anders; E. Roberts, Lydia; Isidore G. Totanes, Francis ; Hart, Sarah; J. Merrick, Catherine

Plasmodium falciparum GBP2 is a telomere-associated protein that binds to G-quadruplex DNA and RNA Thumbnail


Authors

James Edwards-Smallbone

Anders L. Jensen

Lydia E. Roberts

Francis Isidore G. Totanes

Catherine J. Merrick



Abstract

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.

Journal Article Type Article
Acceptance Date Jan 24, 2022
Publication Date Feb 22, 2022
Journal Frontiers in Cellular and Infection Microbiology
Electronic ISSN 2235-2988
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 12
DOI https://doi.org/10.3389/fcimb.2022.782537
Keywords Plasmodium, malaria, G-quadruplex, telomere, proteomics of isolated chromatin fragments, GBP2
Publisher URL https://www.frontiersin.org/articles/10.3389/fcimb.2022.782537/full

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