The I{kappa}B kinase complex is a regulator of mRNA stability

The IB kinase (IKK) is considered to control gene expression primarily through activation of the transcription factor NF-B. 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.

Source: EMBO Journal - December 14, 2018 Category: Molecular Biology Authors: Mikuda, N., Kolesnichenko, M., Beaudette, P., Popp, O., Uyar, B., Sun, W., Tufan, A. B., Perder, B., Akalin, A., Chen, W., Mertins, P., Dittmar, G., Hinz, M., Scheidereit, C. Tags: Immunology, RNA Biology, Signal Transduction Articles Source Type: research