STING/NET23: a transmembrane shuttle at the nuclear envelope to regulate innate immune responses (360G-Wellcome-109089_Z_15_A)

The innate immune response (IIR) is the cell’s first line of defence against pathogens. STING/NET23, an ER and nuclear envelope (NE) resident transmembrane protein, is a key host cell adaptor involved in IIR signalling. STING/NET23’s role at the ER in triggering signalling cascades in response to cytosolic dsDNA is well understood, but its NE role and its function in response to viral RNA is unclear. Previous work in the lab has indicated novel NE roles for STING/NET23 at the centre of a highly redundant signalling network linking 17 NE specific binding partners to IRF3/7 transcription factors. Moreover, it appears to act as an NPC peripheral channel shuttle, redistributing binding partners involved in IIR signalling upon IIR induction. Intriguingly a number of these partners are known to bind RNA, pointing to a role for STING/NET23 in IIR signalling against RNA viruses. This project aims to assess NPC peripheral channel shuttling of STING/NET23 and its binding partners using super resolution microscopy and identify RNA targets of STING/NET23 partners during viral infection. This could resolve two conundrums in the field regarding transmembrane transport between the nuclear and cytoplasmic faces of the NE and how STING/NET23 is able to mediate IIRs to RNA viruses.