The IκB kinase complex is a regulator of mRNA stability

Nadine Mikuda, Marina Kolesnichenko, Patrick Beaudette, Oliver Popp, Bora Uyar, Wei Sun, Ahmet Bugra Tufan, Björn Perder, Altuna Akalin, Wei Chen, Philipp Mertins, Gunnar Dittmar, Michael Hinz, Claus Scheidereit*

*Corresponding author for this work

    Research output: Contribution to journalArticleResearchpeer-review

    16 Citations (Scopus)

    Abstract

    The IκB kinase (IKK) is considered to control gene expression primarily through activation of the transcription factor NF-κB. However, we show here that IKK additionally regulates gene expression on post-transcriptional level. IKK interacted with several mRNA-binding proteins, including a Processing (P) body scaffold protein, termed enhancer of decapping 4 (EDC4). IKK bound to and phosphorylated EDC4 in a stimulus-sensitive manner, leading to co-recruitment of P body components, mRNA decapping proteins 1a and 2 (DCP1a and DCP2) and to an increase in P body numbers. Using RNA sequencing, we identified scores of transcripts whose stability was regulated via the IKK-EDC4 axis. Strikingly, in the absence of stimulus, IKK-EDC4 promoted destabilization of pro-inflammatory cytokines and regulators of apoptosis. Our findings expand the reach of IKK beyond its canonical role as a regulator of transcription.

    Original languageEnglish
    Article numbere98658
    JournalEMBO Journal
    Volume37
    Issue number24
    DOIs
    Publication statusPublished - 14 Dec 2018

    Keywords

    • EDC4
    • IKK
    • P bodies
    • RNA stability
    • post-transcriptional regulation

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