Coordinated regulation of synthesis and stability of RNA during the acute TNF-induced proinflammatory response
Coordinated regulation of synthesis and stability of RNA during the acute TNF-induced proinflammatory response
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DOI：
10.1073/pnas.1219192110
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发表时间：
2013-02-05
影响因子：
11.1
通讯作者：
Ljungman, Mats
中科院分区：
文献类型：
--
作者：
Paulsen, Michelle T.;Veloso, Artur;Ljungman, Mats
稳态基因表达是通过表观遗传调控、转录因子、微小 RNA (miRNA) 和 RNA 结合蛋白协调 RNA 的合成和衰减。在这里，我们提出了溴尿苷标记和测序 (Bru-Seq) 以及溴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性肿瘤坏死因子 (TNF) 后的 RNA 合成和稳定性的全基因组变化。人类细胞的炎症反应涉及基因表达的快速而剧烈的变化，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的调控。与稳态总 RNA 分析相比，使用 Bru-Seq 和 BruChase-Seq 对 RNA 合成和稳定性进行组合分析可以更深入地了解基因调控机制，并且应该在许多生物环境中有用。
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.