Exploration of Zinc finger CCCH domain-containing protein 11A’s role in mammalian cell NFkB Pathway

Abstract: ZC3H11A (ZC3) protein has been reported to be part of the TREX (TRanscription-EXport) nuclear export system for mammalian cells. According to our previous publication, ZC3 not only plays an unelucidated role in the TREX complex, but also supports the growth of several human nucleus replicating virus, such as influenza virus, adenovirus (HAdV), herpes simplex virus and HIV. We thought to further elucidate the role of ZC3 in immunological stress based on previous observations that ZC3 was upregulated in stress condition. Our previous experiment tested the effect of knocking out ZC3 in HeLa cell then stimulating the cells with IL-1β to induce immunological stress. It showed that IL-1β stimulated ZC3 knockout Hela cells produce more than double fold IL6 compared to IL-1β stimulated HeLa Cas 9 wild type. Since IL-6 is downstream of NFkB signalling pathway, we aimed to explore a possible role of ZC3 protein in mammalian cell’s NFkB pathway. Our primary results showed that NFkB pathway might be more upregulated in ZC3 KO cells than in wild type HeLa Cas9 cells. This up-regulation was found to be correlated to defective IkBα inhibitory mRNA biogenesis in knockout cells. Our results indicate that ZC3 might play a role in IkBα inhibitory mRNA biogenesis, process, and/or export. Further work is needed to describe the exact role of ZC3 in IKBα mRNA biogenesis.