title: Malaria parasites possess a telomere repeat-binding protein that shares ancestry with transcription factor IIIA.
abstract: 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.
authors.affiliation: Swiss Tropical and Public Health Institute, Basel 4051, Switzerland.|University of Basel, Basel 4003, Switzerland.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Bertschi
authors.affiliation: Department of Molecular Biology, Radboud University, Nijmegen 6525 GA, The Netherlands.
authors.forename: Christa G
authors.initials: CG
authors.lastname: Toenhake
authors.affiliation: Hospital for Sick Children, Toronto M5G 0A4, Canada.|Department of Biochemistry, University of Toronto, Toronto M5S 1A8, Canada.
authors.forename: Angela
authors.initials: A
authors.lastname: Zou
authors.affiliation: Swiss Tropical and Public Health Institute, Basel 4051, Switzerland.|University of Basel, Basel 4003, Switzerland.
authors.forename: Igor
authors.initials: I
authors.lastname: Niederwieser
authors.affiliation: Department of Molecular Biology, Radboud University, Nijmegen 6525 GA, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Henderson
authors.affiliation: Biozentrum, University of Basel, Basel 4056, Switzerland.
authors.forename: Suzette
authors.initials: S
authors.lastname: Moes
authors.affiliation: Biozentrum, University of Basel, Basel 4056, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Jenoe
authors.affiliation: Hospital for Sick Children, Toronto M5G 0A4, Canada.|Department of Biochemistry, University of Toronto, Toronto M5S 1A8, Canada.|Department of Molecular Genetics, University of Toronto, Toronto M5S 1A8, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Parkinson
authors.affiliation: Department of Molecular Biology, Radboud University, Nijmegen 6525 GA, The Netherlands.
authors.forename: Richard
authors.initials: R
authors.lastname: Bartfai
authors.affiliation: Swiss Tropical and Public Health Institute, Basel 4051, Switzerland.|University of Basel, Basel 4003, Switzerland.
authors.forename: Till S
authors.initials: TS
authors.lastname: Voss
mesh_terms: D019143:Evolution, Molecular; D016778:Malaria, Falciparum / Q000235:genetics*; D011485:Protein Binding; D016615:Telomere / Q000378:metabolism; D034501:Telomere-Binding Proteins / Q000235:genetics*; D035582:Transcription Factor TFIIIA / Q000235:genetics; D016335:Zinc Fingers
chemical_list: D034501:Telomere-Binding Proteins; D035582:Transcription Factor TFIIIA