Abstract

Ribosomopathies are a group of disorders caused by mutations in ribosomal proteins or ribosome biogenesis factors. Despite the ubiquitous requirement for ribosomes in all cells, these disorders manifest as tissue-specific developmental abnormalities, bone marrow failure and an increased predisposition to cancer. A hallmark of ribosomopathies is the paradox of cellular hypo- to hyperproliferation, whereby defective ribosome biogenesis initially activates the p53-mediated stress response, leading to cell-cycle arrest, apoptosis, and impaired tissue growth but subsequently promotes the emergence of cells that bypass these checkpoints and undergo malignant transformation. This mini-review aims to summarize the current understanding of ribosomopathies. The first section provides an overview of ribosome structure, biogenesis, and function, followed by a discussion of the phenotypic spectrum of ribosomopathies and their underlying genetic mutations. The review then examines the paradox of cellular hypo- to hyperproliferation and the molecular mechanisms proposed to explain this phenomenon. Given the role of ribosomopathies in a wide spectrum of clinical diseases, a deeper knowledge of the major molecular pathways, genetic changes and pathogenic mechanisms would facilitate translational research and promote the development of tailored therapeutic approaches.

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