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Global regulation via modulation of ribosome pausing by the ABC-F protein EttA

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  • Farès Ousalem

    (Institut de Biologie Physico-Chimique
    Université Paris Saclay, Institut de Cancérologie Gustave Roussy)

  • Saravuth Ngo

    (Institut de Biologie Physico-Chimique)

  • Thomas Oïffer

    (Institut de Biologie Physico-Chimique)

  • Amin Omairi-Nasser

    (Institut de Biologie Physico-Chimique)

  • Marion Hamon

    (FR550)

  • Laura Monlezun

    (Institut de Biologie Physico-Chimique)

  • Grégory Boël

    (Institut de Biologie Physico-Chimique)

Abstract

Having multiple rounds of translation of the same mRNA creates dynamic complexities along with opportunities for regulation related to ribosome pausing and stalling at specific sequences. Yet, mechanisms controlling these critical processes and the principles guiding their evolution remain poorly understood. Through genetic, genomic, physiological, and biochemical approaches, we demonstrate that regulating ribosome pausing at specific amino acid sequences can produce ~2-fold changes in protein expression levels which strongly influence cell growth and therefore evolutionary fitness. We demonstrate, both in vivo and in vitro, that the ABC-F protein EttA directly controls the translation of mRNAs coding for a subset of enzymes in the tricarboxylic acid (TCA) cycle and its glyoxylate shunt, which modulates growth in some chemical environments. EttA also modulates expression of specific proteins involved in metabolically related physiological and stress-response pathways. These regulatory activities are mediated by EttA rescuing ribosomes paused at specific patterns of negatively charged residues within the first 30 amino acids of nascent proteins. We thus establish a unique global regulatory paradigm based on sequence-specific modulation of translational pausing.

Suggested Citation

  • Farès Ousalem & Saravuth Ngo & Thomas Oïffer & Amin Omairi-Nasser & Marion Hamon & Laura Monlezun & Grégory Boël, 2024. "Global regulation via modulation of ribosome pausing by the ABC-F protein EttA," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50627-z
    DOI: 10.1038/s41467-024-50627-z
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    References listed on IDEAS

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