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

The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules.
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DOI:
10.1038/ni.1699
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发表时间:
2009-03
期刊:
影响因子:
30.5
通讯作者:
--
中科院分区:
医学1区
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--
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炎症反应在起始刺激后以可再现和有组织的方式随时间推移而发生。在这里,我们表明,在培养的小鼠成纤维细胞中激活的基因在细胞因子肿瘤坏死因子(TNF)的反应可以大致分为三组,每组具有不同的诱导动力学。而差异转录是重要的,在确定这些基因的分组,差异mRNA的稳定性也产生了强烈的影响,在某些情况下,压倒转录控制元件的基因表达的时间顺序。早期表达的mRNA转录物在其3′-非翻译区含有丰富的AU富集元件,而后期表达的mRNA转录物含有较少的AU富集元件。因此,mRNA的稳定性和转录控制,基因的两个内在特征,控制促炎性精氨酸诱导的基因表达的动力学。
The inflammatory response plays out over time in a reproducible and organized manner after an initiating stimulus. Here we showed that the genes activated in cultured mouse fibroblasts in response to the cytokine tumor necrosis factor (TNF) can be divided roughly into three groups, each with different induction kinetics. Whereas differential transcription is important in determining the grouping of these genes, differential mRNA stability also exerted a strong influence—in some cases overriding that of transcriptional control elements—on the temporal order of gene expression. mRNA transcripts expressed early have abundant AU-rich elements in their 3′-untranslated regions whereas those expressed later contain fewer. Thus mRNA stability and transcriptional control, two intrinsic characteristics of genes, control the kinetics of proinflammatory cytokine-induced gene expression.
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