Authors
Nicolini, V. J., Dupart, M., Raffelsberger, W., Vidal-Cruchez, O., Rete, T., Jacquet, K., Brau, F., Abelanet, S., Irondelle, M., Bourdin, A., Durivault, J., Gotorbe, C., Knittel-Obrecht, A., Didier, B., Villa, P., Di Gorgio, C., Mograbi, B., Hubstenberger, A., Hofman, P., Brest, P.
Abstract
Processing bodies (P-bodies) are cytoplasmic, membraneless organelles that play a key role in regulating RNA translation. To identify new pathways controlling their formation, we conducted a Food and Drug Administration (FDA)-approved drug screen. We found that glucocorticoids, among the most prescribed medicines, significantly increase P-body numbers across diverse epithelial cell types. This effect was fully reversible after glucocorticoid withdrawal, illustrating the adaptive dynamics of P-bodies. Using genetic invalidation and rescue approaches, we demonstrated that this accumulation requires the Glucocorticoid Receptor alpha isoform. P-body accumulation was associated with the sequestration of P-body-specific-targeted mRNAs, altering their translation yield. Notably, this translational regulation depends on transcript sequence features rather than abundance, with AU-rich mRNA transcripts being sequestered and GC-rich mRNAs preferentially translated under glucocorticoid treatment. Furthermore, we linked the decrease of LSM14B, a negative regulator of P-bodies, under glucocorticoid treatment to P-body reshaping. Our results reveal that, beyond their known transcriptional activity, prolonged exposure to glucocorticoids influences mRNA post-transcription and translation through a nucleotide composition-based mechanism.
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bioRxiv
The authors list and abstract were imported from bioRxiv on 31 Oct 2025.
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