Document Detail

Induction of human interleukin-1 gene expression by retinoic acid and its regulation at processing of precursor transcripts.
MedLine Citation:
PMID:  8083217     Owner:  NLM     Status:  MEDLINE    
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.
N Jarrous; R Kaempfer
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  269     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1994 Sep 
Date Detail:
Created Date:  1994-10-11     Completed Date:  1994-10-11     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  23141-9     Citation Subset:  IM    
Department of Molecular Virology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
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MeSH Terms
Cells, Cultured
Cycloheximide / pharmacology
Gene Expression Regulation / drug effects*
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
Reg. No./Substance:
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

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