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Translational repression by 4E-T is crucial to maintain the prophase-I arrest in vertebrate oocytes

Author

Listed:
  • Andreas Heim

    (University of Konstanz)

  • Shiya Cheng

    (Max Planck Institute for Multidisciplinary Sciences)

  • Jan Orth

    (University of Konstanz
    University of Konstanz)

  • Florian Stengel

    (University of Konstanz
    University of Konstanz)

  • Melina Schuh

    (Max Planck Institute for Multidisciplinary Sciences
    University of Göttingen)

  • Thomas U. Mayer

    (University of Konstanz
    University of Konstanz)

Abstract

Meiotic maturation of vertebrate oocytes occurs in the near-absence of transcription. Thus, female fertility relies on timely translational activation of maternal transcripts stockpiled in full-grown prophase-I-arrested oocytes. However, how expression of these mRNAs is suppressed to maintain the long-lasting prophase-I arrest remains mysterious. Utilizing fast-acting TRIM-Away, we demonstrate that acute loss of the translation repressor 4E-T triggers spontaneous release from prophase-I arrest in mouse and frog oocytes. This is due to untimely expression of key meiotic drivers like c-Mos and cyclin-B1. Notably, mutant 4E-T associated with premature ovarian insufficiency in women fails to maintain the prophase-I arrest in Xenopus oocytes. We further show that 4E-T association with eIF4E and PATL2 is critical for target mRNA binding and repression. Thus, 4E-T is a central factor in translational repression of mRNAs stockpiled in full-grown oocytes for later activation and, therefore, essential to sustain the oocyte pool throughout the reproductive lifespan of female vertebrates.

Suggested Citation

  • Andreas Heim & Shiya Cheng & Jan Orth & Florian Stengel & Melina Schuh & Thomas U. Mayer, 2025. "Translational repression by 4E-T is crucial to maintain the prophase-I arrest in vertebrate oocytes," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62971-9
    DOI: 10.1038/s41467-025-62971-9
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    References listed on IDEAS

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    1. Sybille Pfender & Vitaliy Kuznetsov & Michał Pasternak & Thomas Tischer & Balaji Santhanam & Melina Schuh, 2015. "Live imaging RNAi screen reveals genes essential for meiosis in mammalian oocytes," Nature, Nature, vol. 524(7564), pages 239-242, August.
    2. Charles R. Harris & K. Jarrod Millman & Stéfan J. Walt & Ralf Gommers & Pauli Virtanen & David Cournapeau & Eric Wieser & Julian Taylor & Sebastian Berg & Nathaniel J. Smith & Robert Kern & Matti Picu, 2020. "Array programming with NumPy," Nature, Nature, vol. 585(7825), pages 357-362, September.
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