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

Manful, T., Fadda, A., and Clayton, C. (2011). The role of the 5'-3' exoribonuclease XRNA in transcriptome-wide mRNA degradation. RNA 17, 2039-2047.

Archer, S.K., Inchaustegui, D., Queiroz, R., and Clayton, C. (2011). The cell cycle regulated transcriptome of Trypanosoma brucei. PLoS One 6, e18425.

Schwede, A., Manful, T., Jha, B.A., Helbig, C., Bercovich, N., Stewart, M and Clayton, C. (2009) The role of deadenylation in the degradation of unstable mRNAs in trypanosomes. Nucleic Acids Res 37, 5511-5528

Archer, S.K., Luu, V.-D., de Queiroz, R.A., Brems, S., Clayton, C. (2009) Trypanosoma brucei PUF9 regulates mRNAs for proteins involved in replicative processes over the cell cycle. PLOS Pathogens 5, e1000565

Queiroz, R., Benz, C., Fellenberg K., Hoheisel, J.D. and Clayton, C. (2009) Transcriptome analysis of differentiating trypanosomes reveals the existence of multiple post-transcriptional regulons. BMC Genomics 10, 495

Schwede, A, Ellis, L, Luther, J., Carrington, M., Stoecklin, G. and Clayton, C.E. (2008) A role for Caf1 in mRNA de-adenylation 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 bloodstream-form Trypanosoma brucei. J. Biol. Chem. 283, 2495-2507