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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Droll, D., Minia, I., Fadda, A., Singh, A., Stewart, M., Queiroz, R., Clayton, C. (2013) Post-transcriptional regulation of the trypanosome heat shock response by a zinc finger protein. PloS Pathogens, 9, e1003286, doi:10.1371/journal.ppat.1003286
Fadda, A., Färber, V., Droll, D. and Clayton, C. (2013) The roles of 3’-exoribonucleases and the exosome in trypanosome mRNA degradation. RNA 19, 937-947, doi: 10.1261/rna.038430.113
Singh A, Minia I, Droll D, Fadda A, Clayton C, Erben E. (2014) Trypanosome MKT1 and the RNA-binding protein ZC3H11: interactions and potential roles in post-transcriptional regulatory networks. Nucleic Acids Res 42, 4652-68; 10.1093/nar/gkt1416.
Jha, BA, Fadda, A, Merce, C, Mugo, E, Droll, D and Clayton, C. (2014) Depletion of the trypanosome pumilio domain protein PUF2, or some other essential proteins, causes transcriptome changes related to coding region length Eukaryot. Cell 13, 664-74, doi: 10.1128/EC.00018-14
Erben, E, Fadda, A, Lueong, S, Hoheisel, JD and Clayton, C. (2014) Genome-wide discovery of post-transcriptional regulators in Trypanosoma brucei PLoS Pathogens 10, e1004178. doi:10.1371/journal.ppat.1004178
Begolo, D., Erben, E. and Clayton, C. (2014) Drug target identification using a trypanosome over-expression library. Antimicrob Agents Chemother. 58, 6260-4. doi: 10.1128/AAC.03338-14
Fadda, A, Ryten, M, Droll, D, Rojas, F, Färber, V, Haanstra, JR, Bakker, BM, Matthews, K and Clayton, C. (2014) Transcriptome-wide analysis of mRNA decay reveals complex degradation kinetics and suggests a role for co-transcriptional degradation in determining mRNA levels. Mol Microbiol 94, 307-26. doi: 10.1111/mmi.12764
Erben, E, Chakraborty, C, Clayton, C. (2014) The CAF1-NOT complex of trypanosomes. Frontiers Genetics Research Topics 4, 299. doi: 10.3389/fgene.2013.00299
Clayton, C. (2014) Networks of gene expression control in trypanosomes. Mol Biochem Parasitol 195, 96-106.
Clayton, C. (2013) The regulation of trypanosome gene expression by RNA-binding proteins. PLoS Pathogens, 10s.1371/journal.ppat.1003680