AI Article Synopsis
- The study focuses on the impact of the drugs AN7973, acoziborole, and AN11736 on the cleavage and polyadenylation endonuclease CPSF73, particularly in relation to mRNA processing in parasites.
- Both new drug candidates, acoziborole and AN11736, were found to inhibit mRNA processing similar to AN7973, evidenced by lowered spliced mRNA levels and increased accumulation of specific types of unspliced mRNAs.
- However, a short treatment with AN7973 did not notably change the protein interactions associated with CPSF73, suggesting that its immediate effects may be limited in that regard.
Article Abstract
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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9758897 | PMC |
| http://dx.doi.org/10.1186/s13104-022-06258-y | DOI Listing |
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