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Systematic profiling of cytosolic membraneless organelles reveals enrichment of oncogenic mRNA upon oxidative stress

Year: 2026

Type: article

Abstract: Cytosolic mRNA regulation during and after stress is driven by distinct membraneless organelles. However, their compositional and functional dynamics throughout the stress response remain unclear. We combine APEX2-mediated proximity labeling, RNA sequencing, and high-content imaging to map the human P-body and stress granule transcriptomes during oxidative stress and recovery. Our findings reveal that P-bodies undergo extensive compositional remodeling during stress and that these changes persist during stress recovery. P-body-associated mRNAs during stress exhibit increased AU-rich elements and oncogenic content relative to the cytosol. In contrast, stress granule-associated mRNAs closely resemble the cytosol. These results uncover critical differences between P-bodies and stress granules, shedding light on their functional specialization. Our study provides a valuable resource of cytosolic membraneless organelle-associated transcripts and suggests a specialized role for P-bodies in stress adaptation and recovery.

Source: Cell Reports

DOI: 10.1016/j.celrep.2026.117203