AUTHOR=Edwards-Smallbone James , Jensen Anders L. , Roberts Lydia E. , Totañes Francis Isidore G. , Hart Sarah R. , Merrick Catherine J. 

TITLE=Plasmodium falciparum GBP2 Is a Telomere-Associated Protein That Binds to G-Quadruplex DNA and RNA

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.782537

DOI=10.3389/fcimb.2022.782537

ISSN=2235-2988

ABSTRACT=<p>In the early-diverging protozoan parasite <italic>Plasmodium</italic>, few telomere-binding proteins have been identified and several are unique. <italic>Plasmodium</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 <italic>P. falciparum</italic> GBP2 is such a protein. It was identified <italic>via</italic> ‘Proteomics of Isolated Chromatin fragments’, applied here for the first time in <italic>Plasmodium</italic>. <italic>In vitro</italic>, <italic>Pf</italic>GBP2 binds specifically to G-rich telomere repeats in quadruplex form and it can also bind to G-rich RNA. <italic>In vivo</italic>, <italic>Pf</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. <italic>Pf</italic>GBP2 is evidently a multifunctional DNA/RNA-binding factor in <italic>Plasmodium</italic>.</p>