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Identifying and validating the presence of Guanine-Quadruplexes (G4) within the blood fluke parasite Schistosoma mansoni

Craven, Holly M., Bonsignore, Riccardo, Lenis, Vasilis, Santi, Nicolo, Berrar, Daniel, Swain, Martin, Whiteland, Helen, Casini, Angela and Hoffmann, Karl F. 2021. Identifying and validating the presence of Guanine-Quadruplexes (G4) within the blood fluke parasite Schistosoma mansoni. PLoS Neglected Tropical Diseases 15 (2) , e0008770. 10.1371/journal.pntd.0008770

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Abstract

Schistosomiasis is a neglected tropical disease that currently affects over 250 million individuals worldwide. In the absence of an immunoprophylactic vaccine and the recognition that mono-chemotherapeutic control of schistosomiasis by praziquantel has limitations, new strategies for managing disease burden are urgently needed. A better understanding of schistosome biology could identify previously undocumented areas suitable for the development of novel interventions. Here, for the first time, we detail the presence of G-quadruplexes (G4) and putative quadruplex forming sequences (PQS) within the Schistosoma mansoni genome. We find that G4 are present in both intragenic and intergenic regions of the seven autosomes as well as the sex-defining allosome pair. Amongst intragenic regions, G4 are particularly enriched in 3´ UTR regions. Gene Ontology (GO) term analysis evidenced significant G4 enrichment in the wnt signalling pathway (p<0.05) and PQS oligonucleotides synthetically derived from wnt-related genes resolve into parallel and anti-parallel G4 motifs as elucidated by circular dichroism (CD) spectroscopy. Finally, utilising a single chain anti-G4 antibody called BG4, we confirm the in situ presence of G4 within both adult female and male worm nuclei. These results collectively suggest that G4-targeted compounds could be tested as novel anthelmintic agents and highlights the possibility that G4-stabilizing molecules could be progressed as candidates for the treatment of schistosomiasis

Item Type: Article
Date Type: Publication
Status: Published
Schools: Chemistry
Additional Information: This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Publisher: Public Library of Science
ISSN: 1935-2727
Funders: Wellcome Trust
Date of First Compliant Deposit: 25 March 2021
Date of Acceptance: 2 February 2021
Last Modified: 10 Nov 2021 02:11
URI: https://orca.cardiff.ac.uk/id/eprint/140096

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