SUMMARY In metazoa, nuclear pore complexes (NPCs) assemble from disassembled precursors into a reforming nuclear envelope (NE) at the end of mitosis, and into growing intact NEs during interphase. Here, we show by RNAi-mediated knockdown that ELYS, a nucleoporin critical for the recruitment of the essential Nup107/160 complex to chromatin, is required for NPC assembly at the end of mitosis, but not during interphase. Conversely, the transmembrane nucleoporin POM121 is critical for the incorporation of the Nup107/160 complex into new assembly sites specifically during interphase. Strikingly, recruitment of the Nup107/160 complex to an intact NE involves a membrane curvature-sensing domain of its constituent, Nup133, which is not required for post-mitotic NPC formation. Our results suggest that, in organisms with open mitosis, NPCs assemble by two distinct mechanisms to accommodate cell cycle-dependent differences in NE topology.

STING is essential for control of infections and for tumor immunosurveillance, but can also drive pathological inflammation. STING resides on the endoplasmic reticulum (ER), and traffics following stimulation to ERGIC/Golgi where signaling occurs. Although STING ER exit is the rate-limiting step in STING signaling, the mechanism that drives this process is not understood. Here we identify STEEP as a positive regulator of STING signaling. STEEP was associated with STING and promoted trafficking from the ER. This was mediated through stimulation of phosphatidylinositol-3-phosphate (PI3P) production and ER membrane curvature formation, thus inducing COPII-mediated ER-to-Golgi trafficking of STING. Depletion of STEEP impaired STING-driven gene expression in response to virus infection in brain tissue and in cells from patients with STING-associated diseases. Interestingly, STING gain-of-function mutants from patients interacted strongly with STEEP leading to increased ER PI3P levels and membrane curvature. Thus, STEEP enables STING signaling by promoting ER exit.