Cytoplasmic RBMX coordinates selective mRNA translation to suppress senescence in cancer

Although RBMX has been studied primarily as a nuclear RNA-binding protein involved in splicing and genome maintenance, we identify a previously unrecognized cytoplasmic role for RBMX in regulating senescence entry through selective mRNA translation in cancer cells. We show that a reversible methylation-dependent switch promotes RBMX relocalization to the cytoplasm, where RBMX directly engages the eIF3i/eIF3F initiation module to regulate translation initiation. Cytoplasmic RBMX does not globally enhance protein synthesis; instead, it functions as a translation-specificity factor that preferentially promotes translation of oncogenic mRNAs, including YBX1. Disruption of this translational program reduces YBX1 protein output without affecting mRNA abundance, leading to p53-independent induction of p21 and a robust senescence response. These findings establish selective translational control by cytoplasmic RBMX as a decisive upstream mechanism governing senescence fate in cancer cells.