Mutations in RPS19 may affect ribosome function and biogenesis in Diamond Blackfan anemia. Issue 7 (6th June 2022) - Hiregange, Disha‐Gajanan
Abstract : Ribosomes, the cellular organelles translating the genetic code to proteins, are assemblies of RNA chains and many proteins (RPs) arranged in precise fine‐tuned interwoven structures. Mutated ribosomal genes cause ribosomopathies, including Diamond Blackfan anemia (DBA, a rare heterogeneous red‐cell aplasia connected to ribosome malfunction) or failed biogenesis. Combined bioinformatical, structural, and predictive analyses of potential consequences of possibly expressed mutations in eS19, the protein product of the highly mutated RPS19, suggest that mutations in its exposed surface could alter its positioning during assembly and consequently prevent biogenesis, implying a natural selective strategy to avoid malfunctions in ribosome assembly. A search for RPS19 pseudogenes indicated > 90% sequence identity with the wild‐type, hinting at its expression in cases of absent or truncated gene products. Abstract : Diamond Blackfan anemia (DBA) is a rare congenital intrinsic erythroid hypoplasia, associated with mutated ribosomal genes. Combined bioinformatical, structural, and predictive analyses of potential consequences of expressed mutations in eS19, the protein product of the highest mutated RPS19, suggest that its surface‐exposed mutations could alter its positioning and consequently interfere with ribosome biogenesis, implying a natural selective strategy to avoid malfunctioning ribosomes.