| RRC ID |
70370
|
| Author |
Jaako P, Faille A, Tan S, Wong CC, Escudero-Urquijo N, Castro-Hartmann P, Wright P, Hilcenko C, Adams DJ, Warren AJ.
|
| Title |
eIF6 rebinding dynamically couples ribosome maturation and translation.
|
| Journal |
Nat Commun
|
| 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.
|
| Volume |
13(1)
|
| Pages |
1562
|
| Published |
2022-3-23
|
| DOI |
10.1038/s41467-022-29214-7
|
| PII |
10.1038/s41467-022-29214-7
|
| PMID |
35322020
|
| PMC |
PMC8943182
|
| MeSH |
Animals
Leukemia* / metabolism
Mammals / metabolism
Mice
Proteins* / metabolism
Ribosome Subunits, Large, Eukaryotic / genetics
Ribosome Subunits, Large, Eukaryotic / metabolism
Ribosomes / genetics
Ribosomes / metabolism
Shwachman-Diamond Syndrome
|
| IF |
12.121
|
| Resource |
| Drosophila |
8549R-4 |
