LAUSR

Ribosomopathies are human diseases arising from altered ribosome biogenesis and function. The first of these conditions was described over two decades ago [X-linked Dyskeratosis Congenita (Heiss et al., 1998)]; but since then, the list keeps growing (Venturi and Montanaro, 2020). Ribosome biogenesis is an extremely energy demanding and complex cellular process, involving the coordinated activity of hundreds of different factors (proteins and non-coding RNAs) to produce structurally and functionally competent ribosomes (Kressler et al., 2017). Inherited or acquired genetic alterations underpinning ribosomopathies may involve ribosomal proteins (RP) coding genes [e.g., DiamondBlackfan anemia–DBA (Costa et al., 2020)], ribosome assembly factors [e.g., Schwachman-Diamond Syndrome SDS (Thompson et al., 2022)] or proteins involved in rRNA modifications [e.g., X-linked Dyskeratosis Congenita–X-DC (Penzo and Montanaro, 2018)] or processing [e.g., Cartilage-Hair Hypoplasia–CHH (Thiel and Rauch, 2011)]. Interestingly, all inherited ribosomopathies, which by definition arise as a consequence of germline mutations, have common features that are recapitulated as defects in highly proliferating tissues. Although paradoxically, in each disease the ribosome production defect has tissue-specific instead of ubiquitous effects. Even more intriguingly, most of ribosomopathies share an increased cancer susceptibility compared to the general population. Even though these hallmarks of ribosomopathies have been known for several years, the connection between these two apparently opposite features remains unknown. Somatic genetic alterations broadly affecting ribosome biogenesis, are nowadays well known for having an active role in the onset and/or development of multiple cancer types, which can, therefore, be defined as acquired ribosomopathies (Sulima et al., 2017). This is very well matched with the increased cancer risk for patients affected by inherited ribosomopathies suggesting that de-regulation of ribosome biogenesis and function may actively contribute to malignant transformation (Penzo et al., 2019). The cause-effect connections between the genetic defects undermining ribosome biogenesis and the hypoor hyper-proliferative features of ribosomopathies are for the most part, poorly understood. OPEN ACCESS