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急性 TNF 诱导的促炎反应中 RNA 的合成和稳定性的协调调控。

Coordinated regulation of synthesis and stability of RNA during the acute TNF-induced proinflammatory response.

机构信息

Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center and Translational Oncology Program, University of Michigan, Ann Arbor, MI 48109, USA.

出版信息

Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2240-5. doi: 10.1073/pnas.1219192110. Epub 2013 Jan 23.

Abstract

Steady-state gene expression is a coordination of synthesis and decay of RNA through epigenetic regulation, transcription factors, micro RNAs (miRNAs), and RNA-binding proteins. Here, we present bromouride labeling and sequencing (Bru-Seq) and bromouridine pulse-chase and sequencing (BruChase-Seq) to assess genome-wide changes to RNA synthesis and stability in human fibroblasts at homeostasis and after exposure to the proinflammatory tumor necrosis factor (TNF). The inflammatory response in human cells involves rapid and dramatic changes in gene expression, and the Bru-Seq and BruChase-Seq techniques revealed a coordinated and complex regulation of gene expression both at the transcriptional and posttranscriptional levels. The combinatory analysis of both RNA synthesis and stability using Bru-Seq and BruChase-Seq allows for a much deeper understanding of mechanisms of gene regulation than afforded by the analysis of steady-state total RNA and should be useful in many biological settings.

摘要

稳态基因表达是通过表观遗传调控、转录因子、microRNAs(miRNAs)和 RNA 结合蛋白来协调 RNA 的合成和降解。在这里,我们提出溴化尿苷标记和测序(Bru-Seq)以及溴化尿苷脉冲追踪和测序(BruChase-Seq),以评估人成纤维细胞在稳态和暴露于促炎肿瘤坏死因子(TNF)后,对 RNA 合成和稳定性的全基因组变化。人细胞中的炎症反应涉及基因表达的快速和剧烈变化,Bru-Seq 和 BruChase-Seq 技术揭示了转录和转录后水平上基因表达的协调和复杂调控。使用 Bru-Seq 和 BruChase-Seq 对 RNA 合成和稳定性进行组合分析,可以比分析稳态总 RNA 更深入地了解基因调控机制,并且应该在许多生物学环境中都很有用。

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本文引用的文献

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Landscape of transcription in human cells.人类细胞中的转录景观。
Nature. 2012 Sep 6;489(7414):101-8. doi: 10.1038/nature11233.
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Genome-wide analysis of long noncoding RNA stability.全基因组范围内长非编码 RNA 稳定性分析。
Genome Res. 2012 May;22(5):885-98. doi: 10.1101/gr.131037.111. Epub 2012 Mar 9.
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