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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Line
  • Chromatin Immunoprecipitation
  • Computational Biology / methods
  • Fibroblasts / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genome, Human*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Oxidative Stress*
  • Promoter Regions, Genetic
  • Protein Biosynthesis
  • RNA Polymerase II / metabolism
  • RNA Polymerase III / metabolism
  • RNA, Antisense / genetics
  • RNA, Long Noncoding / classification
  • RNA, Long Noncoding / genetics
  • RNA, Messenger / genetics*
  • RNA, Untranslated / genetics*
  • Transcription Factors / metabolism
  • Transcriptome*

Substances

  • RNA, Antisense
  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA, Untranslated
  • Transcription Factors
  • RNA Polymerase II
  • RNA Polymerase III