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TORC1 phosphorylates and inhibits the ribosome preservation factor Stm1 to activate dormant ribosomes

Target of rapamycin complex 1 (TORC1) promotes biogenesis and inhibits the degradation of ribosomes in response to nutrient availability. To ensure a basal supply of ribosomes, cells are known to preserve a small pool of dormant ribosomes under nutrient‐limited conditions. However, the regulation of...

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Autores principales: Shetty, Sunil, Hofstetter, Jon, Battaglioni, Stefania, Ritz, Danilo, Hall, Michael N
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9975950/
https://www.ncbi.nlm.nih.gov/pubmed/36691768
http://dx.doi.org/10.15252/embj.2022112344
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author Shetty, Sunil
Hofstetter, Jon
Battaglioni, Stefania
Ritz, Danilo
Hall, Michael N
author_facet Shetty, Sunil
Hofstetter, Jon
Battaglioni, Stefania
Ritz, Danilo
Hall, Michael N
author_sort Shetty, Sunil
collection PubMed
description Target of rapamycin complex 1 (TORC1) promotes biogenesis and inhibits the degradation of ribosomes in response to nutrient availability. To ensure a basal supply of ribosomes, cells are known to preserve a small pool of dormant ribosomes under nutrient‐limited conditions. However, the regulation of these dormant ribosomes is poorly characterized. Here, we show that upon inhibition of yeast TORC1 by rapamycin or nitrogen starvation, the ribosome preservation factor Stm1 mediates the formation of nontranslating, dormant 80S ribosomes. Furthermore, Stm1‐bound 80S ribosomes are protected from proteasomal degradation. Upon nutrient replenishment, TORC1 directly phosphorylates and inhibits Stm1 to reactivate translation. Finally, we find that SERBP1, a mammalian ortholog of Stm1, is likewise required for the formation of dormant 80S ribosomes upon mTORC1 inhibition in mammalian cells. These data suggest that TORC1 regulates ribosomal dormancy in an evolutionarily conserved manner by directly targeting a ribosome preservation factor.
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spelling pubmed-99759502023-03-02 TORC1 phosphorylates and inhibits the ribosome preservation factor Stm1 to activate dormant ribosomes Shetty, Sunil Hofstetter, Jon Battaglioni, Stefania Ritz, Danilo Hall, Michael N EMBO J Articles Target of rapamycin complex 1 (TORC1) promotes biogenesis and inhibits the degradation of ribosomes in response to nutrient availability. To ensure a basal supply of ribosomes, cells are known to preserve a small pool of dormant ribosomes under nutrient‐limited conditions. However, the regulation of these dormant ribosomes is poorly characterized. Here, we show that upon inhibition of yeast TORC1 by rapamycin or nitrogen starvation, the ribosome preservation factor Stm1 mediates the formation of nontranslating, dormant 80S ribosomes. Furthermore, Stm1‐bound 80S ribosomes are protected from proteasomal degradation. Upon nutrient replenishment, TORC1 directly phosphorylates and inhibits Stm1 to reactivate translation. Finally, we find that SERBP1, a mammalian ortholog of Stm1, is likewise required for the formation of dormant 80S ribosomes upon mTORC1 inhibition in mammalian cells. These data suggest that TORC1 regulates ribosomal dormancy in an evolutionarily conserved manner by directly targeting a ribosome preservation factor. John Wiley and Sons Inc. 2023-01-24 /pmc/articles/PMC9975950/ /pubmed/36691768 http://dx.doi.org/10.15252/embj.2022112344 Text en © 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Articles
Shetty, Sunil
Hofstetter, Jon
Battaglioni, Stefania
Ritz, Danilo
Hall, Michael N
TORC1 phosphorylates and inhibits the ribosome preservation factor Stm1 to activate dormant ribosomes
title TORC1 phosphorylates and inhibits the ribosome preservation factor Stm1 to activate dormant ribosomes
title_full TORC1 phosphorylates and inhibits the ribosome preservation factor Stm1 to activate dormant ribosomes
title_fullStr TORC1 phosphorylates and inhibits the ribosome preservation factor Stm1 to activate dormant ribosomes
title_full_unstemmed TORC1 phosphorylates and inhibits the ribosome preservation factor Stm1 to activate dormant ribosomes
title_short TORC1 phosphorylates and inhibits the ribosome preservation factor Stm1 to activate dormant ribosomes
title_sort torc1 phosphorylates and inhibits the ribosome preservation factor stm1 to activate dormant ribosomes
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9975950/
https://www.ncbi.nlm.nih.gov/pubmed/36691768
http://dx.doi.org/10.15252/embj.2022112344
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