tRNA modification landscapes and impact on protein synthesis

by Elisa Vilardo
Photos by Elisa Vilardo

 

tRNAs are the essential adapter molecules mediating the translation of messenger RNAs. Yet, relatively little is known about the actual tRNA expression landscape and eventual dynamics in different physiological and/or pathological conditions. With up to 20% of nucleotides modified, tRNAs are the most modified RNA molecules in the cell. Remarkably, mutations in the majority of tRNA modification enzymes are associated with diseases, typically characterized by developmental disorders and restricted to specific tissues. These findings suggest that the hypomodification of tRNAs or the consequent depletion of mature tRNAs in correct, functional form may be particularly detrimental in specific developmental stages and/or cellular contexts.

We have established an NGS-based approach to assess tRNA expression and modification, and, using zebrafish as animal model, we found a switch in expressed tRNAs between early and late embryonal stages. Furthermore, we found that tRNA modifications are modulated during embryo development (https://doi.org/10.1101/2024.01.30.575011).

We now aim to gain mechanistic insight in the establishing of differential tRNA expression and modification profiles, and their significance in the process of development and differentiation. We will dissect the contribution of different tRNAs and specific modification enzymes, and their possible link with the establishment of specialized gene expression programs. We will use zebrafish and stem cells as models, and a wide array of state-of-the-art techniques including CRISPR/Cas9-mediated gene editing, and our own established NGS-based analysis pipeline.

 

Together We Thrive: Collaborative Endeavors in RNA Modification Research

Being part of two large consortia of research laboratories focussed on RNA biology and RNA modification, we will extensively cooperate with our collaborators in a vibrant and international research community .

By leveraging the diverse expertise and resources within our collaborative networks, we aspire to unlock novel insights into the multifaceted roles of RNA modification in cellular biology. Through this concerted effort, we aim to contribute to the advancement of scientific knowledge and pave the way for transformative discoveries with profound implications for human health and disease.

With our project, we ultimately aim to enhance our understanding of the distribution of modifications and the regulatory signals controlling the introduction and removal of modifications, the effect of modifications on folding and structure, and the significance of RNA modification in physiology and disease.

We welcome motivated individuals to join us in this intellectual journey, where rigorous inquiry and interdisciplinary collaboration converge to expand the frontiers of scientific discovery. Together, we can explore the complexities of RNA biology and contribute to meaningful advancements in the field. We are participating with this project in one of the PhD Calls at MedUni Vienna, make sure to apply in a timely manner.

This science is funded by the Austrian Science Fund (FWF)