Journal
NUCLEIC ACIDS RESEARCH
Volume 47, Issue 13, Pages 7063-7077Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkz455
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Funding
- Wellcome Trust [100320/Z/12/Z, 203134/Z/16/Z, 097418/Z/11/Z]
- 'MRC Next Generation Optical Microscopy' award [MR/K015869/1]
- 'Wellcome Trust Technology Platform' award [097945/B/11/Z]
- MRC [MR/K015869/1] Funding Source: UKRI
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Post-transcriptional regulons coordinate the expression of groups of genes in eukaryotic cells, yet relatively few have been characterized. Parasitic try-panosomatids are particularly good models for studies on such mechanisms because they exhibit almost exclusive polycistronic, and unregulated, transcription. Here, we identify the Trypanosoma bru-cei 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.
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