NCBP1 stress signaling drives alternative S6K1 splicing inhibiting translation.

Nuclear stress-induced modification of NCBP1 at cysteine 436 causes alternative splicing of over 250 genes, including S6 kinase, leading to translation inhibition.

• Why it matters: Understanding how localized chemical stress signals regulate protein synthesis is crucial for revealing cellular stress responses and their impact on gene expression.
• What they did: The study used precision electrophile generation and genetic code expansion to map subcellular stress responses, identifying NCBP1 modification at C436 as a key event in nuclear stress signaling.
• The result: Modification of NCBP1(C436) disrupted its interaction with SF3A1, promoting alternative splicing of S6 kinase, which in turn strongly inhibits global protein translation, advancing knowledge of stress-induced translational control.