| mRNA turnover in trypanosomes
African Trypanosomes are unicellular eukaryotic parasites. Trypanosomiasis in cattle is a major contributor to malnutrition and poverty in sub-Saharan Africa, and trypanosomes and related parasites cause serious diseases of humans throughout the tropics. The focus of our research is the degradation of messenger RNA. It is now known that mRNA degradation is critical in controlling gene expression in all organisms: for example, in mammals abnormalities in mRNA degradation can cause autoimmune disease and cancer. Trypanosomes are however unique in relying almost exclusively on degradation to control mRNA levels, which makes them an excellent model system to study this process. In the past few years we have devoted considerable effort to the characterising exoribonucleases that digest mRNAs, and have identified different degradation pathways. We have evidence that stable and unstable mRNAs show different patterns of degradation, and that the choice is determined by specific sequences in the non-coding regions of the RNAs. We now focus mainly on RNA-binding proteins that determine mRNA fate.
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Selected Publications
Schwede, A., Manful, T., Jha, B.A., Claudia Helbig, C., Bercovich, N., Stewart, M and Clayton, C. The role of deadenylation in the degradation of unstable mRNAs in trypanosomes. Nucleic Acids Res (in press)
Schwede, A, Ellis, L, Luther, J., Carrington, M., Stoecklin, G. and Clayton, C.E. (2008) A role for Caf1 in mRNA deadenylation and decay in trypanosomes and human cells. Nucleic Acids Res. 36, 3374-3388
Haanstra, JR, Stewart, M, Luu, V-D., van Tuijl, A., Westerhoff, H.V., *Clayton, C.E. and *Bakker, B.M. (2008). Control and regulation of gene expression: quantitative analysis of the expression of phosphoglycerate kinase in bloodsteam-form Trypanosoma brucei. J. Biol. Chem. 283, 2495-2507
Wurst, M., Robles, A. Po, J., Luu, V-D, Brems, S., Marentije, M., Stoitsova, S., Quijada, L., Hoheisel, J., Stewart, M., Hartmann, C. and Clayton, C. (2009) An RNAi screen of the RRM-domain proteins of Trypanosoma brucei. Mol Biochem Parasitol, 163, 61-65.
Hartmann, C., Benz, C., Brems, S., Ellis, L., Luu, V.D., Stewart, M., D'Orso, I., Bushold, C., Fellenberg, K., Frasch, A.C.C., Carrington, M., Hoheisel, J., and Clayton, C.E. (2007) The small trypanosome RNA-binding proteins TbUBP1 and TbUBP2 influence expression of F-box protein mRNAs in bloodstream trypanosomes Eukaryot. Cell. 6, 1964-78
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