Nucleolin and YB-1 are required for JNK-mediated interleukin-2 mRNA stabilization during T-cell activation.
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.
Chen
C Y
CY
Department of Pharmacology, University of California San Diego, La Jolla, California 92093, USA.
Gherzi
R
R
Andersen
J S
JS
Gaietta
G
G
Jürchott
K
K
Royer
H D
HD
Mann
M
M
Karin
M
M
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
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