Year: 2017
Type: review
Abstract: Mutations that target the ubiquitous process of ribosome assembly paradoxically cause diverse tissue-specific disorders (ribosomopathies) that are often associated with an increased risk of cancer. Ribosomes are the essential macromolecular machines that read the genetic code in all cells in all kingdoms of life. Following pre-assembly in the nucleus, precursors of the large 60S and small 40S ribosomal subunits are exported to the cytoplasm where the final steps in maturation are completed. Here, I review the recent insights into the conserved mechanisms of ribosome assembly that have come from functional characterisation of the genes mutated in human ribosomopathies. In particular, recent advances in cryo-electron microscopy, coupled with genetic, biochemical and prior structural data, have revealed that the SBDS protein that is deficient in the inherited leukaemia predisposition disorder Shwachman-Diamond syndrome couples the final step in cytoplasmic 60S ribosomal subunit maturation to a quality control assessment of the structural and functional integrity of the nascent particle. Thus, study of this fascinating disorder is providing remarkable insights into how the large ribosomal subunit is functionally activated in the cytoplasm to enter the actively translating pool of ribosomes.
Author: Alan J. Warren
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $1,254
Funders: Wellcome Trust, NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research, National Institute for Health and Care Research, Blood Cancer UK, Medical Research Council, Cambridge Institute for Medical Research, University of Cambridge, NIHR Cambridge Biomedical Research Centre
OpenAlex ID: W2753494561