OCT4 translationally promotes AKT signaling as an RNA-binding protein in stressed pluripotent stem cells

• OCT4 functions as a bona fide RNA-binding protein (RBP) in human pluripotent stem cells (PSCs), binding to 5'-UTR, 3'-UTR, and CDS regions of mRNAs. • OCT4 promotes translation initiation of AKT1 and other PI3K/AKT pathway genes via IRES-mediated mechanisms under stress conditions, enhancing cell survival. • Disrupting the OCT4/5'-UTR interaction on AKT1 mRNA increases PSC susceptibility to oxidative stress-induced apoptosis and biases differentiation toward ectoderm and endoderm. • These findings identify OCT4 as a critical anti-stress translational regulator, offering new insights into PSC survival mechanisms and potential therapeutic targets.