Selective inhibition of RNA polymerase I transcription as a potential approach to treat African trypanosomiasis

LE Kerry; EE Pegg; DP Cameron; J Budzak; G Poortinga; KM Hannan; RD Hannan; G Rudenko

Journal article

Selective inhibition of RNA polymerase I transcription as a potential approach to treat African trypanosomiasis

LE Kerry, EE Pegg, DP Cameron, J Budzak, G Poortinga, KM Hannan, RD Hannan, G Rudenko

Plos Neglected Tropical Diseases | PUBLIC LIBRARY SCIENCE | Published : 2017

DOI: 10.1371/journal.pntd.0005432

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Abstract

Trypanosoma brucei relies on an essential Variant Surface Glycoprotein (VSG) coat for survival in the mammalian bloodstream. High VSG expression within an expression site body (ESB) is mediated by RNA polymerase I (Pol I), which in other eukaryotes exclusively transcribes ribosomal RNA genes (rDNA). As T. brucei is reliant on Pol I for VSG transcription, we investigated Pol I transcription inhibitors for selective anti-trypanosomal activity. The Pol I inhibitors quarfloxin (CX-3543), CX-5461, and BMH-21 are currently under investigation for treating cancer, as rapidly dividing cancer cells are particularly dependent on high levels of Pol I transcription compared with nontransformed cells. In..

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University of Melbourne Researchers

Gretchen Poortinga Author

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Awarded by Wellcome Trust

Funding Acknowledgements

LEK is funded by a BBSRC DTP PhD studentship (http://www.bbsrc.ac.uk), GR is a Wellcome Senior Fellow in the Basic Biomedical Sciences (https://wellcome.ac.uk). Research in the Hannan lab is supported by a National Health and Medical Research Council (NHMRC) of Australia project grant (1100654) and program grant (1053792) (https:/www.nhmrc.gov.au). RDH was funded by an NHMRC Fellowship (1022402). This research is funded by the Wellcome Trust. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.