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PMID: 19198593 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules.

Nature immunology ·Vol. 10 ·No. 3 ·2009-03-00 ·Pages 281-8

Hao S, Baltimore D

Abstract

The inflammatory response plays out over time in a reproducible and organized way after an initiating stimulus. Here we show that genes activated in cultured mouse fibroblasts in response to the cytokine tumor necrosis factor could be categorized into roughly three groups, each with different induction kinetics. Although differences in transcription were important in determining the grouping of these genes, differences in mRNA stability also exerted a strong influence on the temporal order of gene expression, in some cases overriding that of transcriptional control elements. Transcripts of mRNA expressed early had abundant AU-rich elements in their 3' untranslated regions, whereas those expressed later had fewer. Thus, mRNA stability and transcriptional control, two intrinsic characteristics of genes, control the kinetics of gene expression induced by proinflammatory cytokines.

MeSH Terms
3T3 Cells Animals Cluster Analysis Dactinomycin/pharmacology Gene Expression Profiling Gene Expression Regulation Humans Inflammation/genetics,metabolism Inflammation Mediators/metabolism Macrophages/metabolism Mice Mice, Inbred C57BL Oligonucleotide Array Sequence Analysis RNA Stability RNA, Messenger/drug effects,metabolism Tumor Necrosis Factor-alpha/metabolism
Chemicals
Inflammation Mediators RNA, Messenger Tumor Necrosis Factor-alpha Dactinomycin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Hao Shengli
Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
Baltimore David
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1699
Published
2009-03-00
Epub
2009-00-08
Pages
281-8
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC2775040
Subset
IM
Grants
NIGMS NIH HHS · R01 GM039458 · United States
NIGMS NIH HHS · R01 GM039458-24 · United States
NIGMS NIH HHS · 2R01GM039458 · United States
Databases
GEO
GSE14071
Corrections
CommentIn
PMID: 19221551
External Links
PubMed source DOI: 10.1038/ni.1699 PMC Full Text View journal details
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