title: Contrasting expression patterns of coding and noncoding parts of the human genome upon oxidative stress.
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.
authors.affiliation: Division of Genome and Gene Expression Data analysis, Bioinformatics Institute A*STAR (Agency for Science, Technology and Research), 138671, Singapore.
authors.forename: Antonis
authors.initials: A
authors.lastname: Giannakakis
authors.affiliation: 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.
authors.forename: Jingxian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Division of Genome and Gene Expression Data analysis, Bioinformatics Institute A*STAR (Agency for Science, Technology and Research), 138671, Singapore.
authors.forename: Piroon
authors.initials: P
authors.lastname: Jenjaroenpun
authors.affiliation: Institute of Medical Biology, A*STAR (Agency for Science, Technology and Research), 138673, Singapore.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Nama
authors.affiliation: 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.
authors.forename: Norliyana
authors.initials: N
authors.lastname: Zainolabidin
authors.affiliation: Division of Cancer Genetics and Therapeutics, Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), 138673, Singapore.
authors.forename: Mei Yee
authors.initials: MY
authors.lastname: Aau
authors.affiliation: Division of Genome and Gene Expression Data analysis, Bioinformatics Institute A*STAR (Agency for Science, Technology and Research), 138671, Singapore.
authors.forename: Aliaksandr A
authors.initials: AA
authors.lastname: Yarmishyn
authors.affiliation: Division of Genome and Gene Expression Data analysis, Bioinformatics Institute A*STAR (Agency for Science, Technology and Research), 138671, Singapore.
authors.forename: Candida
authors.initials: C
authors.lastname: Vaz
authors.affiliation: Division of Genome and Gene Expression Data analysis, Bioinformatics Institute A*STAR (Agency for Science, Technology and Research), 138671, Singapore.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Ivshina
authors.affiliation: Division of Genome and Gene Expression Data analysis, Bioinformatics Institute A*STAR (Agency for Science, Technology and Research), 138671, Singapore.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Grinchuk
authors.affiliation: 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.
authors.forename: Mathijs
authors.initials: M
authors.lastname: Voorhoeve
authors.affiliation: 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.
authors.forename: Leah A
authors.initials: LA
authors.lastname: Vardy
authors.affiliation: 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.
authors.forename: Prabha
authors.initials: P
authors.lastname: Sampath
authors.affiliation: 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.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Kuznetsov
authors.affiliation: Division of Genome and Gene Expression Data analysis, Bioinformatics Institute A*STAR (Agency for Science, Technology and Research), 138671, Singapore.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Kurochkin
authors.affiliation: 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.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Guccione
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology / Q000379:methods; D005347:Fibroblasts / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012319:RNA Polymerase II / Q000378:metabolism; D012320:RNA Polymerase III / Q000378:metabolism; D016372:RNA, Antisense / Q000235:genetics; D062085:RNA, Long Noncoding / Q000145:classification / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D022661:RNA, Untranslated / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome
chemical_list: D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; D014157:Transcription Factors; D012319:RNA Polymerase II; D012320:RNA Polymerase III