Telomere repeat-binding factors (TRFs) are essential components of the molecular machinery that regulates telomere function. TRFs are widely conserved across eukaryotes and bind duplex telomere repeats via a characteristic MYB-type domain. Here, we identified the telomere repeat-binding protein PfTRZ in the malaria parasite Plasmodium falciparum, a member of the Alveolate phylum for which TRFs have not been described so far. PfTRZ lacks an MYB domain and binds telomere repeats via a C2H2-type zinc finger domain instead. In vivo, PfTRZ binds with high specificity to the telomeric tract and to interstitial telomere repeats upstream of subtelomeric virulence genes. Conditional depletion experiments revealed that PfTRZ regulates telomere length homeostasis and is required for efficient cell cycle progression. Intriguingly, we found that PfTRZ also binds to and regulates the expression of 5S rDNA genes. Combined with detailed phylogenetic analyses, our findings identified PfTRZ as a remote functional homologue of the basic transcription factor TFIIIA, which acquired a new function in telomere maintenance early in the apicomplexan lineage. Our work sheds unexpected new light on the evolution of telomere repeat-binding proteins and paves the way for dissecting the presumably divergent mechanisms regulating telomere functionality in one of the most deadly human pathogens.
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Mapping and functional analysis of heterochromatin protein 1 phosphorylation in the malaria parasite Plasmodium falciparum
Scientific Reports Open Access 13 November 2019
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The authors thank R. Sauerwein for providing the anti-Pfs16 antibody and S. Hiller for providing the pGB1 plasmid. This work was supported by the Swiss National Science Foundation (grant nos. PP00P3_130203 and 31003A_143916), the OPO and Rudolf Geigy Foundations, the Novartis Foundation for Medical-Biological Research (grant no. 14A33), the Natural Sciences and Engineering Research Council of Canada (no. RGPIN-2014-06664) and the Netherlands Organization for Scientific Research (no. NWO-Vidi 864.11.007).
The authors declare no competing financial interests.
Supplementary Figures 1-6 and Supplementary Tables 1-4. (PDF 1905 kb)
This file lists all proteins and peptides identified by Mascot and SEQUEST HT searches of the results obtained from LC-MS/MS analysis of nuclear proteins affinity-purified using immobilised Tel6mer DNA (worksheet 1) or scrTel6mer DNA (negative control) (worksheet 2). (XLSX 310 kb)
This file lists the processed microarray data. (XLSX 693 kb)
This file groups all 1488 C2H2-type ZnF proteins of the protein similarity network (Fig. 5a) into clusters of related sequences. (XLSX 31 kb)
This file contains a multiple alignment of all sequences contained in the sequence similarity network of 1488 C2H2-type ZnF proteins (Fig. 5a). (TXT 302 kb)
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Bertschi, N., Toenhake, C., Zou, A. et al. Malaria parasites possess a telomere repeat-binding protein that shares ancestry with transcription factor IIIA. Nat Microbiol 2, 17033 (2017). https://doi.org/10.1038/nmicrobiol.2017.33