Stage BSIB 2022-2023

Ribosome biogenesis is a highly complex essential process shared by all living beings. It is driven by a combined action on ribosomal RNA of ribosomal proteins, RNases, modification enzymes, and assembly factors, many of which are deeply conserved and critical for viability and human health. We have recently characterised one such factor, called YbeY, which is wide-spread from bacteria to humans. YbeY is essential for the assembly of bacterial, chloroplastic and mitochondrial small ribosomal subunits, without which translation is hardly possible. Therefore, deletion of ybeY is often lethal or results in extreme phenotypes, such as slow growth and stress sensitivity (E. coli), or a complete inability to respire (human).

We and others uncovered some key aspects of the molecular mechanism employed by YbeY. In human mitochondria, YBEY, in complex with a cancer- and mitochondrial disease-related protein p32, serves to recruit the ribosomal protein uS11 and incorporate it into the mitochondrial small subunit. This step is critical to generate initiation-competent mitoribosomes and, consequently, to produce essential proteins of the respiratory chain. Excitingly, our recent data suggest that we share this ribosome assembly mechanism with all other YbeY-containing species, from bacteria to protists to plants and other animals. Moreover, YbeY seems to act as an enzyme installing an unusual chemical modification in uS11, which is strictly necessary for ribosome functionality.

In this project, we will address the possible enzymatic mechanism of YbeY. Using a wide variety of biochemical techniques, advanced mass spectrometry analyses, microbial and human cell genetics and microscopy approaches, we will dissect the key determinants of this unique reaction to understand how such a small chemical change results in far-reaching, life-essential consequences across bacterial (E. coli) and eukaryotic (human cells) systems.