Projects per year
Abstract
Post-transcriptional regulons coordinate the expression of groups of genes in eukaryotic cells, yet relatively few have been characterized. Parasitic trypanosomatids are particularly good models for studies on such mechanisms because they exhibit almost exclusive polycistronic, and unregulated, transcription. Here, we identify the Trypanosoma brucei ZC3H39/40 RNA-binding proteins as regulators of the respiratome; the mitochondrial electron transport chain (complexes I-IV) and the FoF1-ATP synthase (complex V). A high-throughput RNAi screen initially implicated both ZC3H proteins in variant surface glycoprotein (VSG) gene silencing. This link was confirmed and both proteins were shown to form a cytoplasmic ZC3H39/40 complex. Transcriptome and mRNA-interactome analyses indicated that the impact on VSG silencing was indirect, while the ZC3H39/40 complex specifically bound and stabilized transcripts encoding respiratome-complexes. Quantitative proteomic analyses revealed specific positive control of >20 components from complexes I, II and V. Our findings establish a link between the mitochondrial respiratome and VSG gene silencing in bloodstream form T. brucei. They also reveal a major respiratome regulon controlled by the conserved trypanosomatid ZC3H39/40 RNA-binding proteins.
Original language | English |
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Pages (from-to) | 7063-7077 |
Number of pages | 15 |
Journal | Nucleic Acids Research |
Volume | 47 |
Issue number | 13 |
Early online date | 25 May 2019 |
DOIs | |
Publication status | Published - 26 Jul 2019 |
Keywords
- Electron-transport
- metabolism
- post-transcription
- translation
- ZC3H39
- ZC3H40
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Dive into the research topics of 'A post-transcriptional respiratome regulon in trypanosomes'. Together they form a unique fingerprint.Projects
- 5 Finished
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Wellcome Centre for Anti-Infectives Research
Cook, S. (Investigator), De Rycker, M. (Investigator), Fairlamb, A. (Investigator), Ferguson, M. (Investigator), Field, M. (Investigator), Gilbert, I. (Investigator), Gray, D. (Investigator), Horn, D. (Investigator), Pawlowic, M. C. (Investigator), Read, K. (Investigator), Wyatt, P. (Investigator) & Wyllie, S. (Investigator)
1/04/17 → 31/03/25
Project: Research
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High-Throughput Decoding of Virulence Mechanisms in African Trypanosomes (Senior Investigator Award)
Horn, D. (Investigator)
1/09/13 → 29/02/20
Project: Research
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Strategic Award: Wellcome Trust Technology Platform
Blow, J. (Investigator), Lamond, A. (Investigator) & Owen-Hughes, T. (Investigator)
1/01/13 → 30/09/18
Project: Research