We aim to understand how chemical modifications in the tRNA anticodon shape translation accuracy and speed. Foremost, we investigate how specific enzymes target specific sites in specific tRNAs and how they catalyse complex modification reactions. Emerging evidence links abnormal anticodon modifications to neurodegenerative diseases and cancer, highlighting diagnostic and therapeutic potential in targeting these pathways for future medicine.

tRNA modifications outside the anticodon loop, located in the D- and T-loops, variable loop, and acceptor stem, are crucial for tRNA stability and proper folding. These chemical changes, mainly caused by methylations and pseudouridinylation, reinforce base stacking, stabilize the structural core, and promote correct tertiary interactions. Thereby these modifications support the three-dimensional folding process and canonical L-shaped conformation of tRNA. We aim to characterize the specific modifying enzymes across eukaryotes, study their site specificity and analyse their intricate network of interconnections. Finally, we quantify the effects on the individual tRNAs by novel biophysical methods and visualize the changes by structural biology.

Cells use ribosomes and tRNA molecules to translate codon-encoded mRNA information into nascent peptide chains. Translating ribosomes are complex macromolecular machines organized into two separate subunits, each composed of folded rRNA and ribosomal proteins (RPs) across all species. Chemical modifications and sequence variants of rRNA play key roles in protein synthesis by affecting the structure of these RNAs, by modulating decoding, and by influencing ribosomal efficiency. Recent advances in sequencing-based detection methods have expanded our ability to map these moieties across RNA molecules in diverse cellular states. Our works aims to understand the mechanisms that lead to the site-specific introduction of rRNA modifications and their functional consequences across species.