RT Journal Article
SR Electronic
T1 eIF6 rebinding dynamically couples ribosome maturation and translation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.09.06.459071
DO 10.1101/2021.09.06.459071
A1 Pekka Jaako
A1 Alexandre Faille
A1 Shengjiang Tan
A1 Chi C. Wong
A1 Norberto Escudero-Urquijo
A1 Pablo Castro-Hartmann
A1 Penny Wright
A1 Christine Hilcenko
A1 David J. Adams
A1 Alan J. Warren
YR 2021
UL http://biorxiv.org/content/early/2021/09/06/2021.09.06.459071.abstract
AB 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 leukaemia 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. Here, we show 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. Our data reveal that ribosome maturation and recycling are dynamically coupled by a mechanism that is disrupted in an inherited leukaemia predisposition disorder.Competing Interest StatementThe authors have declared no competing interest.