Glucocorticoids Modulate mRNA Translation Fate Through P-Body Dynamics
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.
Show 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.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- An integrated stress response-independent role of GCN2 prevents excessive ribosome biogenesis and mRNA translation 96%
- ERLIN1/2 scaffolds bridge TMUB1 and RNF170 and restrict cholesterol esterification to regulate the secretory pathway 95%
- The type of DNA damage response after Decitabine treatment depends on the level of DNMT activity 94%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- The proximity-based protein interaction landscape of the transcription factor p65 NF-kappaB/RELA and its gene-regulatory logics 95%
- The breast cancer oncogene IKKε coordinates mitochondrial function and serine metabolism 95%
- Pervasive compartment-specific regulation of gene expression during homeostatic synaptic scaling 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.