title: Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation.
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.
authors.affiliation: Department of Pharmacology, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: C Y
authors.initials: CY
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Gherzi
authors.forename: J S
authors.initials: JS
authors.lastname: Andersen
authors.forename: G
authors.initials: G
authors.lastname: Gaietta
authors.forename: K
authors.initials: K
authors.lastname: Jürchott
authors.forename: H D
authors.initials: HD
authors.lastname: Royer
authors.forename: M
authors.initials: M
authors.lastname: Mann
authors.forename: M
authors.initials: M
authors.lastname: Karin
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D003593:Cytoplasm / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000235:genetics; D006207:Half-Life; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D048031:JNK Mitogen-Activated Protein Kinases; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; D000097796:Nucleolin
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D048031:JNK Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D051839:NFI Transcription Factors; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; D000097796:Nucleolin; C070856:YBX1 protein, human