Ribosomes: From conserved origin to functional/medical mobility and heterogeneity

Ribosomes, the molecular machines that translate the genetic code from mRNA into proteins in all living cells, are highly structurally conserved across all domains of life and hence are believed to have evolved from a structurally unified pocket. Initially perceived as uniform cellular factories for protein synthesis, currently, ribosomes have emerged as more complex entities. Structural, medical and biochemical studies, including ours, have revealed significant variability in their compositions across tissues, species, functions and developmental stages, highlighting their multifunctional potential. Moreover, the diversity of ribosomes, their components and their associated biological factors challenge the traditional perception of uniform interactions under various conditions, including stress, and expose their mobility and heterogeneity. Evidence for their functional diversity can be seen even in modifications of ribosomal genes, where minor changes may play critical roles under stress or may lead to diseases called ribosomopathies, including Diamond-Blackfan anaemia, some types of cancer and Alzheimer's disease. Thus, through in-depth structural explorations, we improve the understanding of the mechanisms regulating protein biosynthesis in response to various environmental stressors. These findings should potentially reshape the perceptions of the various ribosomal roles. This article is part of the discussion meeting issue 'Ribosome diversity and its impact on protein synthesis, development and disease'.