Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation

• Published in: Genes & development 2000-05, Vol.14 (10), p.1236-1248
• Main Authors: Chen, C Y, Gherzi, R, Andersen, J S, Gaietta, G, Jürchott, K, Royer, H D, Mann, M, Karin, M
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Base Sequence; CCAAT-Enhancer-Binding Proteins; Cytoplasm - chemistry; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - isolation & purification; DNA-Binding Proteins - metabolism; Enzyme Activation; Gene Expression Regulation - genetics; Half-Life; Humans; Interleukin-2 - genetics; JNK Mitogen-Activated Protein Kinases; Jun protein; Jurkat Cells; Lymphocyte Activation; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase Kinases - metabolism; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Molecular Sequence Data; Mutation - genetics; NFI Transcription Factors; Nuclear Proteins; Nucleolin; Phosphoproteins - chemistry; Phosphoproteins - genetics; Phosphoproteins - isolation & purification; Phosphoproteins - metabolism; Precipitin Tests; Protein Binding; Research Paper; Response Elements - genetics; RNA Stability; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-Binding Proteins - chemistry; RNA-Binding Proteins - genetics; RNA-Binding Proteins - isolation & purification; RNA-Binding Proteins - metabolism; T-Lymphocytes - cytology; T-Lymphocytes - enzymology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transcription Factors; Y-Box-Binding Protein 1; YB-1 protein
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.14.10.1236

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.