To gain further insight into the underlying mechanism of NEAT1 function we initially interrogated a human proteome microarray16 consisting of over 16,000 different full-length human proteins (Supplementary Table 1). This analysis identified, among others, members of the potassium channel-interacting family, including KCNAB2 (Fig. 1a,b), as high confidence protein binding partners for NEAT1. These proteins are known to reduce neuronal excitability in order to protect neurons from excessive activity1718 and were previously implicated in epileptic seizure activity1920. After validating that KCNAB2 (Fig. 1c) and KCNIP1 (Supplementary Fig. 1) proteins indeed directly bound NEAT1 in the neuroblastoma cell-line SH-SY5Y by native RNA immunoprecipitation, we found that activation of SH-SY5Y cells by depolarization with 50 mM KCl results in a significant and transient cytoplasmic enrichment of KCNAB2 (Fig. 1d) with a corresponding significant nuclear decrease (Supplementary Fig. 2a) and a significant reduction in NEAT1 transcript after 1 and 3 hours (Supplementary Fig. 2b). We validated that the SH-SY5Y cells were activated following KCl administration via the expected increase in transcript levels of immediate early genes (IEGs) FOS and ARC (Supplementary Fig. 3). Furthermore,
