Mutations in RPS19 may affect ribosome function and biogenesis in Diamond Blackfan anemia

Disha Gajanan Hiregange, Andre Rivalta, Ada Yonath, Ella Zimmerman, Anat Bashan, Hagith Yonath*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1419-1434
Number of pages16
JournalFEBS Open Bio
Volume12
Issue number7
DOIs
StatePublished - Jul 2022

Funding

FundersFunder number
Kimmelman Center for Macromolecular Assemblies
Martin S. and Helen Kimmel Professorial Chair
Seventh Framework Programme322581
European Research Council
Weizmann Institute of Science

    Keywords

    • DBA
    • RPS19
    • eS19
    • genetic mutations
    • ribosomes
    • ribosomopathies

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