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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Base Sequence
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CCAAT-Enhancer-Binding Proteins*
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Cytoplasm / chemistry
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / isolation & purification
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DNA-Binding Proteins / metabolism*
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Enzyme Activation
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Gene Expression Regulation / genetics
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Half-Life
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Humans
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Interleukin-2 / genetics*
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JNK Mitogen-Activated Protein Kinases
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Jurkat Cells
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Lymphocyte Activation*
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MAP Kinase Signaling System
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism*
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Molecular Sequence Data
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Mutation / genetics
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NFI Transcription Factors
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Nuclear Proteins
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Nucleolin
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Phosphoproteins / chemistry
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Phosphoproteins / genetics
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Phosphoproteins / isolation & purification
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Phosphoproteins / metabolism*
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Precipitin Tests
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Protein Binding
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RNA Stability*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA-Binding Proteins / chemistry
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / isolation & purification
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RNA-Binding Proteins / metabolism*
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Response Elements / genetics
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T-Lymphocytes / cytology
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T-Lymphocytes / enzymology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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Transcription Factors*
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Y-Box-Binding Protein 1
Substances
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CCAAT-Enhancer-Binding Proteins
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DNA-Binding Proteins
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Interleukin-2
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NFI Transcription Factors
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Nuclear Proteins
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Phosphoproteins
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RNA, Messenger
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RNA-Binding Proteins
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Transcription Factors
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Y-Box-Binding Protein 1
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YBX1 protein, human
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase Kinases