Transcription poisoning by Topoisomerase I is controlled by gene length, splice sites, and miR-142-3p.
Transcription poisoning by Topoisomerase I is controlled by gene length, splice sites, and miR-142-3p.
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DOI：
10.1158/0008-5472.can-12-3504
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发表时间：
2013-08-01
期刊：
影响因子：
11.2
通讯作者：
Pommier Y
中科院分区：
文献类型：
--
作者：
Solier S;Ryan MC;Martin SE;Varma S;Kohn KW;Liu H;Zeeberg BR;Pommier Y
Topoisomerase I (Top1) relaxes DNA supercoiling by forming transient cleavage complexes (Top1cc) up- and down-stream of transcription complexes. Top1cc can be trapped by carcinogenic and endogenous DNA lesions and by camptothecins resulting in transcription blocks. Here, we undertook genome-wide analysis of camptothecin-treated cells at exon resolution. RNA samples from HCT116 and MCF7 cells were analyzed with the Affy Exon array platform, allowing high resolution mapping along 18,537 genes. Long genes that are highly expressed were the most susceptible to down-regulation, whereas short genes were preferentially up-regulated. Along the body of genes, down-regulation was most important toward the 3’-end, and increased with the number of exon-intron junctions. Ubiquitin and RNA degradation-related pathway genes were selectively down-regulated. Parallel analysis of microRNA with the Agilent miRNA microarray platform revealed that miR-142-3p was highly induced by camptothecin. More than 10% of the down-regulated genes were targets of this p53-dependent microRNA. Our study demonstrates the profound impact of Top1cc on transcription elongation, especially at exon-intron junctions and on transcript stability by microRNA miR-142-3p up-regulation.
