Mechanisms of mitochondrial RNA maturation

by Anna Franziska Finke née Logar
Doctoral thesis
Date of Examination:2025-11-27
Date of issue:2026-01-06
Advisor:Prof. Dr. Hauke Hillen
Referee:Prof. Dr. Hauke Hillen
Referee:Dr. Alex Faesen
Referee:Prof. Dr. Henning Urlaub
Referee:Prof. Dr. Kai Tittmann
Referee:Dr. Ricarda Richter-Dennerlein
Referee:Prof. Dr. Marina Rodnina
Persistent Address: http://dx.doi.org/10.53846/goediss-11726

 

 

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Abstract

English

Cellular energy production is essential for sustaining life and is largely enabled by the presence of a functional respiratory chain in mitochondria. The proper assembly and function of this system are crucial for cellular metabolism, and malfunctions of the mitochondrial “powerhouse” lead to severe disorders. Mitochondrial function depends on the coordinated expression of the mitochondrial genome, which encodes essential subunits of the respiratory chain. Despite its importance, the mechanisms regulating mitochondrial RNA metabolism and translation remain incompletely understood. The first part of this thesis focuses on mitochondrial RNA metabolism, investigating factors that regulate RNA stability, folding, and maturation. High-resolution structures of RNA-binding complexes were determined, providing insight into how these complexes recognize diverse mitochondrial transcripts while retaining specificity. Functional and structural analyses support a model in which these factors coordinate RNA handling and delivery for efficient translation. The second part investigates the transition from mitoribosome biogenesis to translation initiation. The role of the GTPase and assembly factor MTG3 in small mitoribosomal subunit (mtSSU) maturation was characterized using biochemical and structural analyses. Seven cryo-EM structures of mtSSU assembly and (pre-)translation initiation intermediates were determined, showing that MTG3 remains bound during translation initiation to prevent premature subunit joining and to serve as a quality-control checkpoint. Functional data support these structural observations, establishing a model in which mtSSU assembly is coupled to, rather than strictly separated from, translation initiation. Together, these studies provide complementary insights into mitochondrial RNA metabolism and ribosome assembly, advancing the understanding of mitochondrial gene expression and its regulation.
Keywords: RNA metabolism; Mitochondria; RNA-binding proteins; Protein complexes; Structural biology