The IκB kinase complex is a regulator of mRNA stability
Authors
- N. Mikuda
- M. Kolesnichenko
- P. Beaudette
- O. Popp
- B. Uyar
- W. Sun
- A.B. Tufan
- B. Perder
- A. Akalin
- W. Chen
- P. Mertins
- G. Dittmar
- M. Hinz
- C. Scheidereit
Journal
- EMBO Journal
Citation
- EMBO J 37 (24): e98658
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.