Ribosomopathies: There’s strength in numbers

Ribosomopathies are a group of human disorders most commonly caused by ribosomal protein haploinsufficiency or defects in ribosome biogenesis. These conditions manifest themselves as physiological defects in specific cell and tissue types. We review current molecular models to explain ribosomopathie...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2017-11, Vol.358 (6363), p.608-608
Main Authors: Mills, Eric W., Green, Rachel
Format: Article
Language:English
Subjects:
Anemia
Anemia, Diamond-Blackfan - genetics
Anemia, Diamond-Blackfan - metabolism
Animal models
Apoptosis
Asplenia
Biosynthesis
Bone marrow
Brain
Cell activation
Cell cycle
Cell Cycle Checkpoints
Defects
Diamonds
Disorders
Evolution
Footprinting
Gene expression
Graphical representations
Haploinsufficiency
Heterogeneity
Homeostasis
Humans
Hypotheses
Mathematical models
Microprocessors
Models, Biological
Molecular modelling
Mutation
Organ Specificity
p53 Protein
Platelets
Protein Biosynthesis
Protein synthesis
Proteins
REVIEW SUMMARY
Ribonucleic acid
Ribosomal DNA
Ribosomal proteins
Ribosomal Proteins - genetics
Ribosomes
Ribosomes - genetics
Ribosomes - metabolism
RNA
Sensitivity
Signal transduction
Signaling
Tissues
Transfer RNA
Translation
Tumor Suppressor Protein p53 - metabolism
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Summary:Ribosomopathies are a group of human disorders most commonly caused by ribosomal protein haploinsufficiency or defects in ribosome biogenesis. These conditions manifest themselves as physiological defects in specific cell and tissue types. We review current molecular models to explain ribosomopathies and attempt to reconcile the tissue specificity of these disorders with the ubiquitous requirement for ribosomes in all cells. Ribosomopathies as a group are diverse in their origins and clinical manifestations; we use the well-described Diamond-Blackfan anemia (DBA) as a specific example to highlight some common features. We discuss ribosome homeostasis as an overarching principle that governs the sensitivity of specific cells and tissue types to ribosomal protein mutations. Mathematical models and experimental insights rationalize how even subtle shifts in the availability of ribosomes, such as those created by ribosome haploinsufficiency, can drive messenger RNA-specific effects on protein expression. We discuss recently identified roles played by ribosome rescue and recycling factors in regulating ribosome homeostasis.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aan2755