Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation
- Ching-Yi Chen1,5,
- Roberto Gherzi1,5,
- Jens S. Andersen2,
- Guido Gaietta3,
- Karsten Jürchott4,
- Hans-Dieter Royer4,
- Matthias Mann2, and
- Michael Karin1,6
- 1Department of Pharmacology, University of California San Diego, La Jolla, California 92093 USA; 2Protein Interaction Laboratory, University of Southern Denmark-Odense, DK-5230 Odense M, Denmark; 3Department of Neuroscience, University of California San Diego, La Jolla, California 92093 USA; 4Department of Medical Genetics, Max-Delbruck Center for Molecular Medicine, 13122 Berlin, Germany
Abstract
Regulated mRNA turnover is a highly important process, but its mechanism is poorly understood. Using interleukin-2 (IL-2) mRNA as a model, we described a role for the JNK-signaling pathway in stabilization of IL-2 mRNA during T-cell activation, acting via a JNK response element (JRE) in the 5′ untranslated region (UTR). We have now identified two major RNA-binding proteins, nucleolin and YB-1, that specifically bind to the JRE. Binding of both proteins is required for IL-2 mRNA stabilization induced by T-cell activation signals and for JNK-induced stabilization in a cell-free system that duplicates essential features of regulated mRNA decay. Nucleolin and YB-1 are required for formation of an IL-2 mRNP complex that responds to specific mRNA stabilizing signals.
