TY - JOUR
T1 - Contrasting expression patterns of coding and noncoding parts of the human genome upon oxidative stress
AU - Giannakakis, Antonis
AU - Zhang, Jingxian
AU - Jenjaroenpun, Piroon
AU - Nama, Srikanth
AU - Zainolabidin, Norliyana
AU - Aau, Mei Yee
AU - Yarmishyn, Aliaksandr A.
AU - Vaz, Candida
AU - Ivshina, Anna V.
AU - Grinchuk, Oleg V.
AU - Voorhoeve, Mathijs
AU - Vardy, Leah A.
AU - Sampath, Prabha
AU - Kuznetsov, Vladimir A.
AU - Kurochkin, Igor V.
AU - Guccione, Ernesto
N1 - Funding Information:
We thank A*STAR shared facilities for technical support, Xiaoan Ruan and the GIS Genome Sequencing Team for help with the SOLiD and Solexa high-throughput sequencing, Rory Johnson for design of the custom microarray, Anna Ferrer Salvador for assistance with microarray experiment, Anisa Banu Bte Abdul Rahim for technical assistance with polysome profiling and Vivek Tanavde for help in analysis of custom microarray data. This work was supported by Bioinformatics Institute and Institute of Molecular and Cell Biology, A*STAR. EG, PJ, NS and AG acknowledge support from JCO Grant No. 13302RG061. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
PY - 2015/5/29
Y1 - 2015/5/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84930613539&partnerID=8YFLogxK
U2 - 10.1038/srep09737
DO - 10.1038/srep09737
M3 - Article
C2 - 26024509
AN - SCOPUS:84930613539
SN - 2045-2322
VL - 5
JO - Scientific Reports
JF - Scientific Reports
M1 - 9737
ER -