| Induction of human interleukin-1 gene expression by retinoic acid and its regulation at processing of precursor transcripts. | |
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MedLine Citation:
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PMID: 8083217 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Retinoic acid (RA), we show, induces in peripheral blood mononuclear cells a transient wave of newly transcribed, unstable interleukin-1 alpha (IL-1 alpha) and IL-1 beta mRNA. Tumor necrosis factor-alpha mRNA, by contrast, is expressed in multiple waves. IL-1 genes are primary targets for RA. Most IL-1 beta gene transcription induced by RA fails to yield mature mRNA. Instead, precursor transcripts accumulate, detected by ribonuclease protection analysis. The flow of precursors into IL-1 beta mRNA becomes inhibited during induction. When translation is blocked, e.g. by cycloheximide, expression of IL-1 beta mRNA is superinduced by 2 orders of magnitude. Superinduction is dependent on transcription, yet is unaccompanied by increased primary transcription or mRNA stability. Instead, processing of unstable IL-1 beta precursor transcripts into mature mRNA is greatly facilitated. Control is not narrowly localized within precursors: splicing of distinct exons and intron excision are enhanced by cycloheximide. Pre-mRNA processing thus is a limiting step in RA-induced IL-1 beta gene expression. This regulation is specific for RA: when induced by phorbol ester, IL-1 beta gene expression is also superinduced by cycloheximide but that response is accompanied by enhanced mRNA stability. Thus, IL-1 beta gene transcription is induced by RA, yet, unlike for other primary target genes, mRNA expression is regulated at pre-mRNA processing. |
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Authors:
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N Jarrous; R Kaempfer |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 269 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1994 Sep |
Date Detail:
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Created Date: 1994-10-11 Completed Date: 1994-10-11 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 23141-9 Citation Subset: IM |
Affiliation:
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Department of Molecular Virology, Hebrew University-Hadassah Medical School, Jerusalem, Israel. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Cells, Cultured Cycloheximide / pharmacology Gene Expression Regulation / drug effects* Humans Interleukin-1 / genetics*, metabolism RNA Precursors / genetics, metabolism* RNA Processing, Post-Transcriptional* RNA, Messenger / biosynthesis, genetics, metabolism Tetradecanoylphorbol Acetate / pharmacology Transcription, Genetic / drug effects Tretinoin / pharmacology* Tumor Necrosis Factor-alpha / genetics |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-1; 0/RNA Precursors; 0/RNA, Messenger; 0/Tumor Necrosis Factor-alpha; 16561-29-8/Tetradecanoylphorbol Acetate; 302-79-4/Tretinoin; 66-81-9/Cycloheximide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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