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

Author

Listed:
  • Javier Encinar del Dedo

    (University of Salamanca)

  • M. Belén Suárez

    (CSIC
    University of Salamanca)

  • Rafael López-San Segundo

    (University of Salamanca)

  • Alicia Vázquez-Bolado

    (University of Salamanca)

  • Jingjing Sun

    (Singapore-MIT Alliance for Research and Technology)

  • Natalia García-Blanco

    (University of Salamanca)

  • Patricia García

    (CSIC
    University of Salamanca)

  • Pauline Tricquet

    (University of Namur)

  • Jun-Song Chen

    (Vanderbilt University School of Medicine)

  • Peter C. Dedon

    (Singapore-MIT Alliance for Research and Technology
    Massachusetts Institute of Technology)

  • Kathleen L. Gould

    (Vanderbilt University School of Medicine)

  • Elena Hidalgo

    (Universitat Pompeu Fabra)

  • Damien Hermand

    (University of Namur
    The Francis Crick Institute)

  • Sergio Moreno

    (University of Salamanca)

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.

Suggested Citation

  • Javier Encinar del Dedo & M. Belén Suárez & Rafael López-San Segundo & Alicia Vázquez-Bolado & Jingjing Sun & Natalia García-Blanco & Patricia García & Pauline Tricquet & Jun-Song Chen & Peter C. Dedo, 2024. "The Greatwall-Endosulfine-PP2A/B55 pathway regulates entry into quiescence by enhancing translation of Elongator-tunable transcripts," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-55004-4
    DOI: 10.1038/s41467-024-55004-4
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    References listed on IDEAS

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    1. Atsushi Matsuda & Yuji Chikashige & Da-Qiao Ding & Chizuru Ohtsuki & Chie Mori & Haruhiko Asakawa & Hiroshi Kimura & Tokuko Haraguchi & Yasushi Hiraoka, 2015. "Highly condensed chromatins are formed adjacent to subtelomeric and decondensed silent chromatin in fission yeast," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    2. Sanki Tashiro & Tetsuya Handa & Atsushi Matsuda & Takuto Ban & Toru Takigawa & Kazumi Miyasato & Kojiro Ishii & Kazuto Kugou & Kunihiro Ohta & Yasushi Hiraoka & Hisao Masukata & Junko Kanoh, 2016. "Shugoshin forms a specialized chromatin domain at subtelomeres that regulates transcription and replication timing," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
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