Regulation of Trypanosoma brucei total and polysomal mRNA during development within its mammalian host

Capewell, P. , Monk, S., Ivens, A., MacGregor, P., Fenn, K., Walrad, P., Bringaud, F., Smith, T. K. and Matthews, K. R. (2013) Regulation of Trypanosoma brucei total and polysomal mRNA during development within its mammalian host. PLoS ONE, 8(6), e67069. (doi: 10.1371/journal.pone.0067069) (PMID:23840587) (PMCID:PMC3694164)

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Abstract

The gene expression of Trypanosoma brucei has been examined extensively in the blood of mammalian hosts and in forms found in the midgut of its arthropod vector, the tsetse fly. However, trypanosomes also undergo development within the mammalian bloodstream as they progress from morphologically ‘slender forms’ to transmissible ‘stumpy forms’ through morphological intermediates. This transition is temporally progressive within the first wave of parasitaemia such that gene expression can be monitored in relatively pure slender and stumpy populations as well as during the progression between these extremes. The development also represents the progression of cells from translationally active forms adapted for proliferation in the host to translationally quiescent forms, adapted for transmission. We have used metabolic labelling to quantitate translational activity in slender forms, stumpy forms and in forms undergoing early differentiation to procyclic forms in vitro. Thereafter we have examined the cohort of total mRNAs that are enriched throughout development in the mammalian bloodstream (slender, intermediate and stumpy forms), irrespective of strain, revealing those that exhibit consistent developmental regulation rather than sample specific changes. Transcripts that cosediment with polysomes in stumpy forms and slender forms have also been enriched to identify transcripts that escape translational repression prior to transmission. Combined, the expression and polysomal association of transcripts as trypanosomes undergo development in the mammalian bloodstream have been defined, providing a resource for trypanosome researchers. This facilitates the identification of those that undergo developmental regulation in the bloodstream and therefore those likely to have a role in the survival and capacity for transmission of stumpy forms.

Item Type:Articles
Additional Information:This work was supported by a Wellcome Trust Programme grant to KM and by a Wellcome Trust Strategic award to the Centre for Immunity, Infection and Evolution at the University of Edinburgh. SM was supported by a studentship from the Medical Research Council, UK.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Capewell, Dr Paul
Authors: Capewell, P., Monk, S., Ivens, A., MacGregor, P., Fenn, K., Walrad, P., Bringaud, F., Smith, T. K., and Matthews, K. R.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2013 Capewell et al.
First Published:First published in PLoS ONE 8(6): e67069
Publisher Policy:Reproduced under a Creative Commons License

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