Sculpting the catalytic core of the ribosome-insights from rare disease

The synthesis of new ribosomes is a fundamental conserved process in all cells. Ribosomes are pre-assembled in the nucleus and subsequently exported to the cytoplasm where they acquire functionality through a series of final maturation steps that include recruitment of the last remaining ribosomal proteins and the removal of inhibitory assembly factors to form the catalytic core (peptidyltransferase centre). Surprisingly, a number of key factors required for late cytoplasmic maturation of the large ribosomal subunit are mutated in the ribosomopathies, a fascinating new class of leukaemia predisposition disorders. I will illustrate how our multidisciplinary approach to understanding the pathogenesis of one such disorder has provided unexpected new insights into the mechanisms of eukaryotic ribosome assembly and its quality control.