Life Sci Alliance. 2026 Oct;pii: e202603806. [Epub ahead of print]9(10):
P-bodies are cytoplasmic membraneless organelles involved in mRNA storage, yet their role in cellular stress responses remains unresolved. Here, we demonstrate that P-bodies are remodeled during the early response to ER stress throughout Drosophila melanogaster oogenesis. Notably, this remodeling occurs within minutes of stress induction and precedes stress granule formation. This early remodeling is characterized by changes in P-body morphology and internal organization and promotes selective mRNA storage. Mechanistically, we find that this process is driven by transcriptional up-regulation of the RNA-binding protein, Bruno 1, downstream of ATF4-dependent stress signaling, thereby establishing a connection between the unfolded protein response and condensate regulation. Consistent with this model, loss of Bruno 1 abolishes, whereas its overexpression enhances, P-body remodeling, demonstrating that stress-induced changes in RNA-binding protein levels can reprogram condensate properties. Together, our findings reveal that P-bodies function as stress-responsive hubs enabling selective preservation of essential mRNAs during ER stress. More broadly, this work uncovers a previously unrecognized mechanism by which stress signaling pathways reorganize cytoplasmic architecture to shape mRNA fate.