NCBP1 stress signaling drives alternative S6K1 splicing inhibiting translation.

NCBP1 stress signaling induces alternative splicing of over 250 genes, including S6 kinase, which inhibits global protein translation in the nucleus.

• Why it matters: Understanding how subcellular stress signals regulate protein synthesis is crucial for revealing mechanisms of cellular response and adaptation, yet the specific molecular pathways remain unclear.
• What they did: The study used localized electrophile generation and genetic code expansion to examine four subcellular locales, identifying nuclear-targeted electrophile stress as the only one to stall translation, and pinpointed NCBP1(C436) modification as key.
• The result: Modification of NCBP1 at cysteine 436 disrupts its interaction with SF3A1, leading to alternative splicing of S6 kinase, which then dominantly inhibits protein synthesis, highlighting a novel stress response pathway.