eIF6 rebinding dynamically couples ribosome maturation and translation.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
23 03 2022
23 03 2022
Historique:
received:
15
10
2021
accepted:
03
03
2022
entrez:
24
3
2022
pubmed:
25
3
2022
medline:
13
4
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35322020
doi: 10.1038/s41467-022-29214-7
pii: 10.1038/s41467-022-29214-7
pmc: PMC8943182
doi:
Substances chimiques
Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1562Subventions
Organisme : Wellcome Trust
ID : 105914/Z/14/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 100140
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T012412/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Department of Health
ID : BRC-1215-20014
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206171/Z/17/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202905/Z/16/Z
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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