Lost in translation

Ribosomes are tremendously elaborate cellular machines that translate messenger RNAs into proteins. Ribosome dysregulation causes specific pathological conditions called ribosomopathies, a collection of rare genetic disorders characterized by anaemia together with growth retardation and developmental abnormalities. Although ribosomes are active in all cell types, the predominant clinical manifestation of ribosomopathy is a failure of erythropoiesis, the production of red blood cells. The most studied ribosomopathy is the Diamond-Blackfan Anaemia (DBA), a rare congenital disease, which is characterized by the presence of anaemia and increased susceptibility to cancer in the patients. Approximately 70% of DBA patients are found to harbour mutations in genes that encode ribosomal proteins. However, recent studies have uncovered a group of non-ribosomal proteins that can potentially cause DBA when dysregulated. The group of Kaan Boztug at the St. Anna Childrens Cancer Research Institute (St. Anna CCRI) is now investigating the precise role of these non-ribosomal proteins in ribosome stability, transport, turnover and function. By using a variety of approaches and model systems, this study aims first to comprehensively dissect the function of these non-ribosomal proteins on ribosomal biology, and secondly to investigate their contribution and impact on ribosomopathy syndromes when dysregulated. Unravelling the regulatory roles of these non-ribosomal proteins and their complex interplay with ribosomes under both normal and pathological conditions will shed light on their function in ribosome biology. Furthermore, these studies will provide new strategies for the diagnosis, prevention, treatment and monitoring of ribosome-associated human diseases.