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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Clayton, C. Regulation of gene expression in trypanosomatids: living with polycistronic transcription. (2019) Royal Society Open Biology 9, 190072.
Liu, B, Kamanyi Marucha, K and Clayton, C. The zinc finger proteins ZC3H20 and ZC3H21 stabilise mRNAs encoding membrane proteins and mitochondrial proteins in insect-form Trypanosoma brucei. Mol MIcrobiol., in press. PMID: 31743541 DOI: 10.1111/mmi.14429
Begolo D, Vincent IM, Giordani F, Pöhner I, Witty MJ, Rowan TG, Bengaly Z, Gillingwater K, Freund Y, Wade RC, Barrett MP, and Clayton C. (2018) The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing. PLoS Pathogens 14, e1007315.
Terrao M, Kimanyi Marucha K, Mugo E, Braun J, Droll D, Minia I, Egler F, and Clayton C. 2018) The suppressive cap-binding-complex factor 4EIP is required for normal differentiation. Nucleic Acids Res 46, 8993-9010.
Mulindwa, J, Leiss, K, Ibberson, D, Kamanyi Marucha, K, Helbig, C, Nascimento, L, Silvester, E, Matthews, K, Matovu, E, Enyaru, J and Clayton, C (2018) Transcriptomes of Trypanosoma brucei rhodesiense from sleeping sickness patients, rodents and culture: effects of strain, growth conditions and RNA preparation methods. PLoS Negl Trop Dis 12, e0006280
Minia, I, Clayton, C. (2016) Regulating a post-transcriptional regulator: protein phosphorylation, degradation and translational blockage in control of the trypanosome stress-response RNA-binding protein ZC3H11. PLoS Pathogens 12, e1005514, 10.1371/journal.ppat.1005514
Antwi, E, Haanstra, J, Ramasamy, G, Jensen, B, Droll, D, Rojas, F, Minia, I, Terrao, M, Mercé, C, Matthews, K, Myler, PJ,, Parsons, M and Clayton, C. (2016) Integrative analysis of the Trypanosoma brucei gene expression cascade predicts differential regulation of mRNA processing and unusual control of ribosomal protein expression. BMC Genomics 17, 306, 10.1186/s12864-016-2624-3
Minia I, Mercé C, Terrao M, Clayton C. (2016) Translation regulation and RNA granule ormation after heat shock of procyclic form Trypanosoma brucei: many heat-induced mRNAs are increased during differentiation to mammalian-infective forms. PLoS Negl Trop Dis 10, e0004982142
Mugo E and Clayton C. (2017) Expression of the RNA-binding protein RBP10 promotes the bloodstream-form differentiation state in Trypanosoma brucei. PLoS Pathogens 13, e1006560 10.1371/journal.pntd.0006280.
Mulindwa, J, Mercé, C, Matovu, E, Enyaru, J, Clayton, C. (2015) Transcriptomes of newly-isolated Trypanosoma brucei rhodesiense reveal hundreds of mRNAs that are co-regulated with stumpy-form markers. BMC Genomics 16, 1118
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