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

Andreas Heim (), Shiya Cheng, Jan Orth, Florian Stengel, Melina Schuh and Thomas U. Mayer ()
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Andreas Heim: University of Konstanz
Shiya Cheng: Max Planck Institute for Multidisciplinary Sciences
Jan Orth: University of Konstanz
Florian Stengel: University of Konstanz
Melina Schuh: Max Planck Institute for Multidisciplinary Sciences
Thomas U. Mayer: University of Konstanz

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-62971-9

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