Built differently or defective: can RNA exosomopathies cause ribosome heterogeneity?

The RNA exosome is an essential, evolutionarily conserved ribonuclease required for processing and degradation of key cellular RNAs. The complex maintains RNA homeostasis within every cell by ensuring the proper maturation, quality control and turnover of various RNA species including rRNAs. A growing list of diseases, collectively termed RNA exosomopathies, are caused by mutations in genes encoding structural subunits of the RNA exosome complex. RNA exosomopathies often result in tissue-specific defects, particularly manifesting as neurological disorders, which is intriguing given the ubiquitous functions and expression of the RNA exosome. One such ubiquitous, essential function of the RNA exosome is its involvement in ribosome biogenesis. In this review, we discuss the established connections between the RNA exosome and ribosome biogenesis, exploring the potential mechanisms through which RNA exosomopathies could influence ribosome heterogeneity, leading to aberrant translation and pathogenesis. We highlight the critical need for research in this area that can aid in understanding the complex aetiology of RNA exosomopathies and the future development of therapeutic strategies to mitigate pathology.This article is part of the discussion meeting issue 'Ribosome diversity and its impact on protein synthesis, development and disease'.