The Role of the snR37 H/ACA snoRNP in Ribosome Assembly

Ribosomes are essential machines in our cells that produce all the proteins required for life. Without them, cells could not perform their many vital functions. To work reliably, a ribosome must be assembled with great precision from its components: ribosomal RNA (rRNA), which forms its structural framework, and numerous ribosomal proteins. An important step in this process is the chemical modification of rRNA, including the conversion of the RNA building block uridine into pseudouridine. Small helper complexes called snoRNPs carry out these modifications. snoRNPs consist of short RNA molecules and several proteins that specifically recognize defined sites on the rRNA and chemically modify them. Another crucial step in forming functional ribosomes is the folding of the initially thread-like rRNA into a complex three-dimensional structure. How the cell ensures that the rRNA folds into the correct shape is still largely unknown, but it has long been suspected that snoRNPs might play a role in this process as well. We have now found concrete evidence that a particular snoRNP, called snR37, is indeed important not only for pseudouridylation but also for the formation of the three-dimensional structure of ribosomes. Remarkably, snR37 differs from most known snoRNPs: it contains unique structural elements and additional proteins that are absent in other snoRNPs. We believe that these special features enable snR37 to perform its unique function. Specifically, these additional components appear to give snR37 a scaffold-like role that supports the folding of the rRNA. Our observations suggest that snR37 may act already at the very first stages of ribosome assembly. The goal of our project is to determine when and how snR37 binds to nascent ribosomes, what functions its special components perform, how exactly snR37 assists rRNA folding, and how it is ultimately released once its function is completed, allowing ribosome assembly to proceed. To address these questions, we will study various snR37 mutants, identify its binding partners, and analyze the resulting effects on ribosome formation. The results will provide important insights into fundamental mechanisms of cell biology and deepen our understanding of how ribosomes are built. Alterations or malfunctions of snoRNPs such as snR37 have been linked to diseases including cancer, neurodegenerative disorders, and premature aging. In the long term, our findings may help to clarify the causes of such conditions and open up new avenues for therapeutic strategies. In this way, our project contributes to understanding the molecular foundations of life and their relevance to health and disease.