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

被引:104
作者
Paulsen, Michelle T. [1 ,2 ]
Veloso, Artur [1 ,2 ,3 ]
Prasad, Jayendra [1 ,2 ]
Bedi, Karan [1 ,2 ,4 ]
Ljungman, Emily A. [1 ,2 ]
Tsan, Ya-Chun [1 ,2 ,4 ]
Chang, Ching-Wei [1 ,2 ,5 ]
Tarrier, Brendan [8 ]
Washburn, Joseph G. [8 ]
Lyons, Robert [8 ]
Robinson, Daniel R. [6 ]
Kumar-Sinha, Chandan [6 ]
Wilson, Thomas E. [6 ,7 ]
Ljungman, Mats [1 ,2 ,4 ]
机构
[1] Univ Michigan, Ctr Comprehens Canc, Dept Radiat Oncol, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Translat Oncol Program, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Bioinformat Program, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Ann Arbor, MI 48109 USA
[6] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA
[7] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA
[8] Univ Michigan, DNA Sequencing Core, Ann Arbor, MI 48109 USA
关键词
GENOME-WIDE ANALYSIS; NF-KAPPA-B; POSTTRANSCRIPTIONAL CONTROL; TRANSCRIPTION; INITIATION; RESOLUTION; INDUCTION; CANCER;
D O I
10.1073/pnas.1219192110
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:2240 / 2245
页数:6
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