ena-STUDY-UNIVERSITY OF BERN-04-06-2020-12:42:20:853-109
An Alba-domain protein required for proteome remodeling during differentiation of Trypanosoma brucei
Alba-domain proteins exhibit functions ranging from DNA-binding in Archaea to tRNA processing in mammals and translational control in protozoan parasites. Over the past decade, it has been shown that Alba-domain proteins contribute to developmental regulation in protozoan parasites. Trypanosoma brucei, responsible for human sleeping sickness, progresses through distinct life cycle stages as it cycles between its mammalian and tsetse fly host. T. brucei has 4 Alba-domain proteins that have been shown to interact with each other and with proteins of the translation machinery. Here we describe deletion mutants of two Alba-domain proteins, Alba3 and Alba4, and the requirements for them in bloodstream forms and during the transition to procyclic forms. We show that deletion of Alba3 or Alba4 does not have an effect on parasite's survival as bloodstream forms and that Alba3 and Alba4 are functionally redundant in bloodstream forms. In contrast, only Alba3 can support successful differentiation from the stumpy to the procyclic form. Comparative proteomic and transcriptomic analysis of the Alba3 deletion mutant and wild-type parasites during differentiation, together with polysome profile analysis shows that differentiation regulation by Alba3 is achieved by extensive remodeling of the proteome. In summary, our studies show that Alba3 plays an important role in remodeling the proteome at the level of translation during differentiation of stumpy forms to procyclic forms.
Alba-domain proteins exhibit functions ranging from DNA-binding in Archaea to tRNA processing in mammals and translational control in protozoan parasites. Over the past decade, it has been shown that Alba-domain proteins contribute to developmental regulation in protozoan parasites. Trypanosoma brucei, responsible for human sleeping sickness, progresses through distinct life cycle stages as it cycles between its mammalian and tsetse fly host. T. brucei has 4 Alba-domain proteins that have been shown to interact with each other and with proteins of the translation machinery. Here we describe deletion mutants of two Alba-domain proteins, Alba3 and Alba4, and the requirements for them in bloodstream forms and during the transition to procyclic forms. We show that deletion of Alba3 or Alba4 does not have an effect on parasite's survival as bloodstream forms and that Alba3 and Alba4 are functionally redundant in bloodstream forms. In contrast, only Alba3 can support successful differentiation from the stumpy to the procyclic form. Comparative proteomic and transcriptomic analysis of the Alba3 deletion mutant and wild-type parasites during differentiation, together with polysome profile analysis shows that differentiation regulation by Alba3 is achieved by extensive remodeling of the proteome. In summary, our studies show that Alba3 plays an important role in remodeling the proteome at the level of translation during differentiation of stumpy forms to procyclic forms.