Clinically relevant benzoxaboroles inhibit mRNA processing in Trypanosoma brucei.
Benzoxaboroles
CPSF73
Tandem affinity purification
mRNA processing
Journal
BMC research notes
ISSN: 1756-0500
Titre abrégé: BMC Res Notes
Pays: England
ID NLM: 101462768
Informations de publication
Date de publication:
17 Dec 2022
17 Dec 2022
Historique:
received:
15
07
2022
accepted:
30
11
2022
entrez:
17
12
2022
pubmed:
18
12
2022
medline:
21
12
2022
Statut:
epublish
Résumé
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. 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.
Identifiants
pubmed: 36528767
doi: 10.1186/s13104-022-06258-y
pii: 10.1186/s13104-022-06258-y
pmc: PMC9758897
doi:
Substances chimiques
AN7973
0
AN11736
0
Boron Compounds
0
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
371Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : CL112/26-1
Organisme : HBIGS
ID : none
Informations de copyright
© 2022. The Author(s).
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