A post-transcriptional respiratome regulon in trypanosomes

Anna Trenaman, Lucy Glover, Sebastian Hutchinson, David Horn (Lead / Corresponding author)

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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 languageEnglish
Pages (from-to)7063-7077
Number of pages15
JournalNucleic Acids Research
Volume47
Issue number13
Early online date25 May 2019
DOIs
Publication statusPublished - 26 Jul 2019

Keywords

  • Electron-transport
  • metabolism
  • post-transcription
  • translation
  • ZC3H39
  • ZC3H40

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