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Sci Rep. 2015 May 29;5:9737. doi: 10.1038/srep09737.

Contrasting expression patterns of coding and noncoding parts of the human genome upon oxidative stress.

Author information

1
Division of Genome and Gene Expression Data analysis, Bioinformatics Institute A*STAR (Agency for Science, Technology and Research), 138671, Singapore.
2
1] Division of Cancer Genetics and Therapeutics, Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), 138673, Singapore [2] Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 119074, Singapore.
3
Institute of Medical Biology, A*STAR (Agency for Science, Technology and Research), 138673, Singapore.
4
Division of Cancer Genetics and Therapeutics, Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), 138673, Singapore.
5
1] Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 119074, Singapore [2] Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, 8 College Road, 169857, Singapore.
6
1] Institute of Medical Biology, A*STAR (Agency for Science, Technology and Research), 138673, Singapore [2] School of Biological Sciences, Nanyang Technological University, 138673, Singapore.
7
1] Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 119074, Singapore [2] Institute of Medical Biology, A*STAR (Agency for Science, Technology and Research), 138673, Singapore [3] Program in Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, 8 College Road, 169857, Singapore.
8
1] Division of Genome and Gene Expression Data analysis, Bioinformatics Institute A*STAR (Agency for Science, Technology and Research), 138671, Singapore [2] School of Computer Engineering, Nanyang Technological University, 639798, Singapore.

Abstract

Oxidative stress (OS) is caused by an imbalance between pro- and anti-oxidant reactions leading to accumulation of reactive oxygen species within cells. We here investigate the effect of OS on the transcriptome of human fibroblasts. OS causes a rapid and transient global induction of transcription characterized by pausing of RNA polymerase II (PolII) in both directions, at specific promoters, within 30 minutes of the OS response. In contrast to protein-coding genes, which are commonly down-regulated, this novel divergent, PolII pausing-phenomenon leads to the generation of thousands of long noncoding RNAs (lncRNAs) with promoter-associated antisense lncRNAs transcripts (si-paancRNAs) representing the major group of stress-induced transcripts. OS causes transient dynamics of si-lncRNAs in nucleus and cytosol, leading to their accumulation at polysomes, in contrast to mRNAs, which get depleted from polysomes. We propose that si-lncRNAs represent a novel component of the transcriptional stress that is known to determine the outcome of immediate-early and later cellular stress responses and we provide insights on the fate of those novel mature lncRNA transcripts by showing that their association with polysomal complexes is significantly increased in OS.

PMID:
26024509
PMCID:
PMC4448690
DOI:
10.1038/srep09737
[Indexed for MEDLINE]
Free PMC Article

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