Plasmodium falciparum GBP2 Is a Telomere-Associated Protein That Binds to G-Quadruplex DNA and RNA
Authors
Edwards-Smallbone, James
Jensen, Anders L
Roberts, Lydia E
Totañes, Francis Isidore G
Hart, Sarah R
Merrick, Catherine J
Publication Date
2022-02-22Journal Title
Frontiers in Cellular and Infection Microbiology
Publisher
Frontiers Media SA
Volume
12
Language
en
Type
Article
This Version
VoR
Metadata
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Edwards-Smallbone, J., Jensen, A. L., Roberts, L. E., Totañes, F. I. G., Hart, S. R., & Merrick, C. J. (2022). Plasmodium falciparum GBP2 Is a Telomere-Associated Protein That Binds to G-Quadruplex DNA and RNA. Frontiers in Cellular and Infection Microbiology, 12 https://doi.org/10.3389/fcimb.2022.782537
Abstract
<jats:p>In the early-diverging protozoan parasite <jats:italic>Plasmodium</jats:italic>, few telomere-binding proteins have been identified and several are unique. <jats:italic>Plasmodium</jats:italic> 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 <jats:italic>P. falciparum</jats:italic> GBP2 is such a protein. It was identified <jats:italic>via</jats:italic> ‘Proteomics of Isolated Chromatin fragments’, applied here for the first time in <jats:italic>Plasmodium</jats:italic>. <jats:italic>In vitro</jats:italic>, <jats:italic>Pf</jats:italic>GBP2 binds specifically to G-rich telomere repeats in quadruplex form and it can also bind to G-rich RNA. <jats:italic>In vivo</jats:italic>, <jats:italic>Pf</jats:italic>GBP2 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. <jats:italic>Pf</jats:italic>GBP2 is evidently a multifunctional DNA/RNA-binding factor in <jats:italic>Plasmodium</jats:italic>.</jats:p>
Keywords
Cellular and Infection Microbiology, Plasmodium, malaria, G-quadruplex, telomere, proteomics of isolated chromatin fragments, GBP2
Identifiers
External DOI: https://doi.org/10.3389/fcimb.2022.782537
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334760
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Licence:
http://creativecommons.org/licenses/by/4.0/
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