Die Synthese und Funktion von ZC3H11 bei der Hitze-Schock Antwort in Trypanosoma brucei

• Antragstellerin: Professorin Dr. Christine Elizabeth Clayton
• Fachliche Zuordnung: Parasitologie und Biologie der Erreger tropischer Infektionskrankheiten ; Zellbiologie
• Förderung: Förderung von 2012 bis 2019
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 218732757

• Erstellungsjahr: 2019

Zusammenfassung der Projektergebnisse

We had two main questions: A. How is expression of ZC3H11 regulated in procyclic forms? How is ZC3H11 mRNA translation repressed at 27*C? How is ZC3H11 mRNA translation enhanced at 39*C? How is ZC3H11 proteolysis controlled? B. How does ZC3H11 act during the procyclic heat shock response? Is the mechanism the same as in bloodstream forms at 37°C (MKT1, PBP1, LSM12)? If not, which other interactions are required? For (A), we mapped the regulatory element in great detail. We found that phosphorylation (probably by casein kinase 1.2) influences ZC3H11 degradation, which is reduced by proteasome inhibitors. Various different attempts to identify proteins required for ZC3H11 regulation were, however, unsuccessful. For (B) we took advantage of a new method and showed that mRNAs that are bound by ZC3H11 are preferentially excluded from translationally inactive RNA-protein granules that form after heat shock. Studies of proteins that activate expression in the tethering assay revealed an additional component of the MKT1-PBP1-LSM12 complex (XAC1) and a second homologue of Mkt1, MKT1L.

Projektbezogene Publikationen (Auswahl)

• (2016) Regulating a post-transcriptional regulator: protein phosphorylation, degradation and translational blockage in control of the trypanosome stress-response RNA-binding protein ZC3H11. PLoS Pathogens 12:e1005514
  Minia I, Clayton C
  
• (2016) Translation regulation and RNA granule formation after heat shock of procyclic form Trypanosoma brucei: many heat-induced mRNAs are increased during differentiation to mammalian-infective forms. PLoS Negl Trop Dis 10:e0004982
  Minia I, Merce C, Terrao M, Clayton C
  
• (2018) Stress susceptibility in Trypanosoma brucei lacking the RNA-binding protein ZC3H30. PLoS Negl Trop Dis 12, e0006835
  Chakraborty, C and Clayton, C
  
• (2018) The suppressive cap-binding-complex factor 4EIP is required for normal differentiation. Nucleic Acids Res 46, 8993-9010
  Terrao M, Kamanyi Marucha K, Mugo E, Droll D, Minia I, Egler F, Braun J, Clayton C