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Research article - Peer-reviewed, 2022

ZC3H11A loss of function enhances NF-κB signaling through defective IκBα protein expression

Darweesh, Mahmoud; Younis, Shady; Hajikhezri, Zamaneh; Ali, Arwa; Jin, Chuan; Punga, Tanel; Gupta, Soham; Essand, Magnus; Andersson, Leif; Akusjaervi, Goran


ZC3H11A is a cellular protein associated with the transcription export (TREX) complex that is induced during heat-shock. Several nuclear-replicating viruses exploit the mRNA export mechanism of ZC3H11A protein for their efficient replication. Here we show that ZC3H11A protein plays a role in regulation of NF-kappa B signal transduction. Depletion of ZC3H11A resulted in enhanced NF-kappa B mediated signaling, with upregulation of numerous innate immune related mRNAs, including IL-6 and a large group of interferon-stimulated genes. IL-6 upregulation in the absence of the ZC3H11A protein correlated with an increased NF-kappa B transcription factor binding to the IL-6 promoter and decreased IL-6 mRNA decay. The enhanced NF-kappa B signaling pathway in ZC3H11A deficient cells correlated with a defect in I kappa B alpha inhibitory mRNA and protein accumulation. Upon ZC3H11A depletion The I kappa B alpha mRNA was retained in the cell nucleus resulting in failure to maintain normal levels of the cytoplasmic I kappa B alpha mRNA and protein that is essential for its inhibitory feedback loop on NF-kappa B activity. These findings indicate towards a previously unknown mechanism of ZC3H11A in regulating the NF-kappa B pathway at the level of IkB alpha mRNA export.


ZC3H11A; NF-kB, IkBa; IL6; adenovirus

Published in

Frontiers in Immunology
2022, Volume: 13, article number: 1002823

    UKÄ Subject classification

    Cell Biology

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