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

Hao, Shengli and Baltimore, David (2009) The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules. Nature Immunology, 10 (3). pp. 281-288. ISSN 1529-2908.

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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.

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Baltimore, David0000-0001-8723-8190
Additional Information:© 2009 Nature Publishing Group. Received 18 November 2008; accepted 31 December 2008; published online 8 February 2009. We thank M. Boldin, R. O’Connell, X. Luo and K. Taganov for comments on the manuscript, and A. Balazs (California Institute of Technology) for the plasmid pHAGE2-CMV-eGFP-W. Supported by the National Institutes of Health (2R01GM039458 to D.B.) and the Millard and Muriel Jacobs Genetics and Genomics Laboratory at California Institute of Technology (microarray analysis).
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Millard and Muriel Jacobs Genetics and Genomics LaboratoryUNSPECIFIED
Issue or Number:3
Record Number:CaltechAUTHORS:20090413-083201541
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:13943
Deposited By: Tony Diaz
Deposited On:04 Aug 2009 21:22
Last Modified:03 Oct 2019 00:45

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