MicroRNA analysis suggests an additional level of feedback regulation in the NF-κB signaling cascade
Metrics: PDF 1411 views | HTML 1490 views | ?
Peter Mechtler1,*, Ruchi Singhal1,3,*, Julia V. Kichina1, Jonathan E. Bard2, Michael J. Buck2, Eugene S. Kandel1
1Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA
2Department of Biochemistry, State University of New York, Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, USA
3Cellecta, Inc., Mountain View, CA, USA
*These authors have contributed equally to this work
Eugene S. Kandel, e-mail: firstname.lastname@example.org
Keywords: RIPK1, miR-497, miR-146a, miR-215, IKKβ
Received: April 06, 2015 Accepted: May 05, 2015 Published: May 16, 2015
It is increasingly clear that the biological functions of a transcription factor cannot be fully understood solely on the basis of protein-coding genes that fall under its control. Many transcription factors regulate expression of miRNAs, which affect the cell by modulating translation and stability of mRNAs. The identities and the roles of NF-κB-regulated miRNAs have been attracting research interest for a long time. We revisited this issue in a system with controlled expression of one of the key regulators of NF-κB, RIPK1. Several regulated miRNAs were identified, including miR-146a, miR-215 and miR-497. The miRNAs were also inducible by IL-1β, but not when NF-κB activity was repressed by mutant IκBα. The presence of a miR-497 site was predicted in the 3′-UTR of IKBKB gene, which encodes IKKβ. Using appropriately engineered reporters, we confirmed that this site can be a target of suppressive action of miR-497. Our findings suggest that NF-κB controls expression of a miRNA, which may reduce production of IKKβ. Considering the role of IKKβ in the canonical pathway of NF-κB activation, our observations may indicate a new mechanism that modulates the magnitude of such activation, as well as the propensity of a cell to engage canonical vs. non-canonical pathways.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.