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Dissertation
Diphthamide modified eEF2: Insights into Function, Crosstalk and Disease
(2020)
Diphthamid ist eine posttranslationale Proteinmodifikation eines konservierten Histidins an dem eukaryotischen und archaealen translations-elongations Faktor 2 (eEF2 und aEF2). Obwohl die Diphthamidbiosynthese ein komplexer und gut beschriebener Ablauf ist, gibt es bisher keine detaillierte Beschreibung einer positiven zellulären Funktion der Modifikation.
Dissertation
The Importance of tRNA Modification and SSD1 Status for Protein Homeostasis and Cell Viability
(2022-03)
Chemical modifications of anticodon loop are required to support tRNA function in mRNA decoding and to prevent protein aggregation in the eukaryotic model system Saccharomyces cerevisiae. This work investigates the effects of mutation in the gene encoding the Deg1 pseudouridine synthase. It is known that the mutation of the human DEG1 orthologue PUS3 causes severe neurological and developmental defects, emphasizing the general importance of the modification. However, the exact cellular consequences of deg1/pus3mutation ...
Dissertation
Investigation of the functional synergy and involvement of different tRNA modifications in translational control
(2020-07-02)
Transfer RNAs are essential adapter molecules employed in the translational process and are highly modified all over their structure. Specific modification of the four canonical ribonucleotides (A, U, C, G) is accomplished by various proteins and/or protein complexes, ranging from simple isomerisations (e.g. Ψ) and methylations (e.g. m5C) up to complex chemical structures (e.g. mcm5s2U, ct6A). The functions of tRNA modifications are linked to the specific position and may influence translation by supporting the native ...
Dissertation
The tRNA binding protein Kti12 and its role in the regulation of Elongator complex
(2020-06-08)
[Summary] Kti12 is a conserved eukaryotic protein showing sequence homology to O-phosphoseryltRNA kinase (Pstk), which is required for the synthesis of selenocysteine tRNA. Saccharomyces cerevisiae Kti12 was originally discovered in a genetic screening for resistance against zymocin, a protein toxin produced by Kluyveromyces lactis. The cytotoxicity of zymocin lies in its anticodon nuclease activity, causing tRNA depletion and cell death in sensitive yeast cells. It recognizes and cleaves a particular wobble uridine ...
Dissertation
Functional analyses of Dph1•Dph2 in synthesis of diphthamide, a clinically relevant modification on eEF2
(2024)
Diphthamide is a unique post-translational modification of a conserved histidine on the eukaryotic translation elongation factor 2 (eEF2). During translation elongation, eEF2 induces translocation of codon-anticodon duplexes across the ribosomal decoding center. Diphthamide is involved in fine-tuning of this process by stabilizing the codon-anticodon duplex and maintaining reading frame accuracy. Initially, diphthamide was identified as the target for diphtheria toxin, enabling ADP-ribosylation of eEF2 and resulting ...