The Greatwall-Endosulfine-PP2A/B55 pathway regulates entry into quiescence by enhancing translation of Elongator-tunable transcripts

Encinar del Dedo, Javier; Suárez, M. Belén; López-San Segundo, Rafael; Vázquez Bolado, Alicia; Sun, Jingjing; García Blanco, Natalia; García, Patrícia; Tricquet, Pauline; Chen, Jun-Song; Dedon, Peter C.; Gould, Kathleen L.; Hidalgo Hernando, Elena; Hermand, Damien; Moreno, Sergio

The Greatwall-Endosulfine-PP2A/B55 pathway regulates entry into quiescence by enhancing translation of Elongator-tunable transcripts

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dc.contributor.author Encinar del Dedo, Javier
dc.contributor.author Suárez, M. Belén
dc.contributor.author López-San Segundo, Rafael
dc.contributor.author Vázquez Bolado, Alicia
dc.contributor.author Sun, Jingjing
dc.contributor.author García Blanco, Natalia
dc.contributor.author García, Patrícia
dc.contributor.author Tricquet, Pauline
dc.contributor.author Chen, Jun-Song
dc.contributor.author Dedon, Peter C.
dc.contributor.author Gould, Kathleen L.
dc.contributor.author Hidalgo Hernando, Elena
dc.contributor.author Hermand, Damien
dc.contributor.author Moreno, Sergio
dc.date.accessioned 2025-02-05T07:08:35Z
dc.date.available 2025-02-05T07:08:35Z
dc.date.issued 2024
dc.description.abstract Quiescent cells require a continuous supply of proteins to maintain protein homeostasis. In fission yeast, entry into quiescence is triggered by nitrogen stress, leading to the inactivation of TORC1 and the activation of TORC2. In this study, we demonstrate that the Greatwall-Endosulfine-PPA/B55 pathway connects the downregulation of TORC1 with the upregulation of TORC2, resulting in the activation of Elongator-dependent tRNA modifications crucial for sustaining the translation programme during entry into quiescence. This mechanism promotes U34 and A37 tRNA modifications at the anticodon stem loop, enhancing translation efficiency and fidelity of mRNAs enriched for AAA versus AAG lysine codons. Notably, several of these mRNAs encode TORC1 inhibitors, TORC2 activators, tRNA modifiers, and proteins necessary for telomeric and subtelomeric functions. Therefore, we propose a mechanism by which cells respond to nitrogen stress at the level of translation, involving a coordinated interplay between tRNA epitranscriptome and biased codon usage.
dc.description.sponsorship This work was funded by the Spanish Ministry of Science and Innovation-MCIN (grants BFU2017-88335-R and PID2020-115929RB-I00) and from the Castile and Leon government (grants CSI259P20, CSI010P23 and IBFG Unit of Excellence programs CLU-2017-03 and CL-EI-2021-08 co-funded by the P.O. Feder of Castile and Leon 14-20 and European Union ERDF “Europe drives our growth”) to S.M., and by the National Research Foundation of Singapore under its Singapore-MIT Alliance for Research and Technology Antimicrobial Resistance Interdisciplinary Research Group to J.S. and P.D.. The work in K.L.G.´s lab was supported by the National Institutes of Health R35GM131799, and in D.H.´s lab by PDR T.0012.14, CDR J.0066.16 and PDR T.0112.21 grants. D.H. is an honorary FNRS Director of Research and was affiliated with the University of Namur until November 23rd, 2023. N.G.-B. and A.V.-B. were funded by XFPU15/03654, BES-2015-073171, predoctoral training contracts. R.L.-S.S. was funded by a predoctoral fellowship from the Castile and Leon government.
dc.format.mimetype application/pdf
dc.identifier.citation Encinar Del Dedo J, Suárez MB, López-San Segundo R, Vázquez-Bolado A, Sun J, García-Blanco N, et al. The Greatwall-Endosulfine-PP2A/B55 pathway regulates entry into quiescence by enhancing translation of Elongator-tunable transcripts. Nat Commun. 2024 Dec 5;15(1):10603. DOI: 10.1038/s41467-024-55004-4
dc.identifier.doi http://dx.doi.org/10.1038/s41467-024-55004-4
dc.identifier.issn 2041-1723
dc.identifier.uri http://hdl.handle.net/10230/69488
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Nat Commun. 2024 Dec 5;15(1):10603
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-88335-R
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-115929RB-I00
dc.rights © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.keyword Nuclear envelope
dc.subject.keyword Nutrient signalling
dc.subject.keyword TOR signalling
dc.subject.keyword tRNAs
dc.title The Greatwall-Endosulfine-PP2A/B55 pathway regulates entry into quiescence by enhancing translation of Elongator-tunable transcripts
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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