Le jeudi 18 septembre 2025, Margaux CLAES présentera l'examen en vue de l’obtention du grade académique de Docteur en Sciences (Collège de doctorat en Biochimie, biologie moléculaire et cellulaire, bioinformatique et modélisation) sous la direction de Franck DEQUIEDT.

Cette épreuve consistera en la défense publique d’une dissertation intitulée :

« New insights into the non-canonical role of the transcription factor FOXMl in mRNA stability regulation ».

Le Jury sera composé de :

Mme C. SADZOT (Présidente), Mmes et MM. F. DEQUIEDT (Promoteur), C. GUEYDAN (ULB), M. LEBRUN, X. RAMBOUT (University of Rochester), I. STRUMAN (Secrétaire).

Summary

Gene expression regulation is a fundamental process in all living cells, governing cellular functions and responses to environmental cues. This regulation begins in the nucleus with the synthesis of a precursor messenger RNA (pre-mRNA), which undergoes maturation, export to the cytoplasm, translation into functional proteins, and degradation. The control of mRNA levels is a crucial aspect of gene expression regulation, achieved through a dynamic balance between mRNA synthesis and degradation. While transcription is a well-characterized process regulated by specific transcription factors binding to defined DNA sequences to modulate mRNA production, mRNA degradation is governed by distinct decay factors that recognize specific mRNA features. Emerging evidence suggests that transcription factors may play a direct role in post-transcriptional gene regulation, including mRNA degradation. In this work, we investigated the transcription factor FOXM1, a key regulator of cell cycle progression at the transcriptional level. Our findings demonstrate that FOXM1 not only modulates gene expression through transcriptional activation but also influences mRNA degradation. Specifically, deep RNA-sequencing analysis revealed that FOXM1 depletion alters the half-lives of hundreds of mRNAs. We further showed that FOXM1 interacts with multiple RNA-binding proteins, including DDX5, DDX17, HuR, and STAU1. Together, FOXM1 and its interacting RBPs cooperate to Promote mRNA decay. Notably, the 3’ untranslated region (3’UTR) of FOXM1 target mRNAs appears to play a critical role in mRNA stability regulation. In particular, we identified CCNY as an mRNA target stabilized upon FOXM1 depletion and demonstrated that its 3’UTR is essential for mRNA stability control. Finally, we showed that FOXM1-mediated regulation of CCNY mRNA stability is important for proper cell cycle progression. Overall, our findings reveal that FOXM1 regulates gene expression not only at the level of transcription but also by modulating mRNA degradation. These results redefine the molecular role of transcription factors and highlight their broader impact on post-transcriptional gene regulation.

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