eIF6 rebinding dynamically couples ribosome maturation and translation.
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Authors
Faille, Alexandre
Tan, Shengjiang
Escudero-Urquijo, Norberto
Castro-Hartmann, Pablo
Wright, Penny
Hilcenko, Christine
Publication Date
2022-03-23Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
13
Issue
1
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Jaako, P., Faille, A., Tan, S., Wong, C. C., Escudero-Urquijo, N., Castro-Hartmann, P., Wright, P., et al. (2022). eIF6 rebinding dynamically couples ribosome maturation and translation.. Nat Commun, 13 (1) https://doi.org/10.1038/s41467-022-29214-7
Abstract
Protein synthesis is a cyclical process consisting of translation initiation, elongation, termination and ribosome recycling. The release factors SBDS and EFL1-both mutated in the leukemia predisposition disorder Shwachman-Diamond syndrome - license entry of nascent 60S ribosomal subunits into active translation by evicting the anti-association factor eIF6 from the 60S intersubunit face. We find that in mammalian cells, eIF6 holds all free cytoplasmic 60S subunits in a translationally inactive state and that SBDS and EFL1 are the minimal components required to recycle these 60S subunits back into additional rounds of translation by evicting eIF6. Increasing the dose of eIF6 in mice in vivo impairs terminal erythropoiesis by sequestering post-termination 60S subunits in the cytoplasm, disrupting subunit joining and attenuating global protein synthesis. These data reveal that ribosome maturation and recycling are dynamically coupled by a mechanism that is disrupted in an inherited leukemia predisposition disorder.
Keywords
Ribosomes, Animals, Mammals, Mice, Leukemia, Proteins, Ribosome Subunits, Large, Eukaryotic, Shwachman-Diamond Syndrome
Sponsorship
Wellcome Trust (202905/Z/16/Z)
Wellcome Trust (206171/Z/17/Z)
Kay Kendall Leukaemia Fund (KKL1246)
MRC (MR/T012412/1)
Blood Cancer UK (21002)
Wellcome Trust (100140/Z/12/Z)
National Institute for Health Research (IS-BRC-1215-20014)
Identifiers
35322020, PMC8943182
External DOI: https://doi.org/10.1038/s41467-022-29214-7
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336404
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