Clinically relevant benzoxaboroles inhibit mRNA processing in Trypanosoma brucei

OBJECTIVE: The cleavage and polyadenylation endonuclease CPSF73 is thought to be the target of the anti-trypanosomal benzoxaboroles AN7973, acoziborole and AN11736. We previously showed that AN7973 inhibits mRNA processing. We here investigated whether the drug candidates acoziborole (for human slee...

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Autores principales: Waithaka, Albina, Clayton, Christine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Research Note
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9758897/
https://www.ncbi.nlm.nih.gov/pubmed/36528767
http://dx.doi.org/10.1186/s13104-022-06258-y
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author Waithaka, Albina
Clayton, Christine
author_facet Waithaka, Albina
Clayton, Christine
author_sort Waithaka, Albina
collection PubMed
description OBJECTIVE: The cleavage and polyadenylation endonuclease CPSF73 is thought to be the target of the anti-trypanosomal benzoxaboroles AN7973, acoziborole and AN11736. We previously showed that AN7973 inhibits mRNA processing. We here investigated whether the drug candidates acoziborole (for human sleeping sickness) and AN11736 (for nagana in cattle) have the same effect. We also affinity purified tagged CPSF73 from parasites without, or after, AN7973 treatment, and analysed differentially co-purified proteins by mass spectrometry. RESULTS: AN11736 and acoziborole both inhibited mRNA processing, as demonstrated by decreased levels of spliced mRNAs and accumulation of di- and tri-cistronic mRNAs from the alpha-beta tubulin locus. Treating the cells with AN7973 for 30 min. did not significantly affect the proteins that copurified with CPSF73. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13104-022-06258-y.
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spelling pubmed-97588972022-12-18 Clinically relevant benzoxaboroles inhibit mRNA processing in Trypanosoma brucei Waithaka, Albina Clayton, Christine BMC Res Notes Research Note OBJECTIVE: The cleavage and polyadenylation endonuclease CPSF73 is thought to be the target of the anti-trypanosomal benzoxaboroles AN7973, acoziborole and AN11736. We previously showed that AN7973 inhibits mRNA processing. We here investigated whether the drug candidates acoziborole (for human sleeping sickness) and AN11736 (for nagana in cattle) have the same effect. We also affinity purified tagged CPSF73 from parasites without, or after, AN7973 treatment, and analysed differentially co-purified proteins by mass spectrometry. RESULTS: AN11736 and acoziborole both inhibited mRNA processing, as demonstrated by decreased levels of spliced mRNAs and accumulation of di- and tri-cistronic mRNAs from the alpha-beta tubulin locus. Treating the cells with AN7973 for 30 min. did not significantly affect the proteins that copurified with CPSF73. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13104-022-06258-y. BioMed Central 2022-12-17 /pmc/articles/PMC9758897/ /pubmed/36528767 http://dx.doi.org/10.1186/s13104-022-06258-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Note
Waithaka, Albina
Clayton, Christine
Clinically relevant benzoxaboroles inhibit mRNA processing in Trypanosoma brucei
title Clinically relevant benzoxaboroles inhibit mRNA processing in Trypanosoma brucei
title_full Clinically relevant benzoxaboroles inhibit mRNA processing in Trypanosoma brucei
title_fullStr Clinically relevant benzoxaboroles inhibit mRNA processing in Trypanosoma brucei
title_full_unstemmed Clinically relevant benzoxaboroles inhibit mRNA processing in Trypanosoma brucei
title_short Clinically relevant benzoxaboroles inhibit mRNA processing in Trypanosoma brucei
title_sort clinically relevant benzoxaboroles inhibit mrna processing in trypanosoma brucei
topic Research Note
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9758897/
https://www.ncbi.nlm.nih.gov/pubmed/36528767
http://dx.doi.org/10.1186/s13104-022-06258-y
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