title: Contributions of transcription and mRNA decay to gene expression dynamics of fission yeast in response to oxidative stress.
abstract: The cooperation of transcriptional and post-transcriptional levels of control to shape gene regulation is only partially understood. Here we show that a combination of two simple and non-invasive genomic techniques, coupled with kinetic mathematical modeling, afford insight into the intricate dynamics of RNA regulation in response to oxidative stress in the fission yeast Schizosaccharomyces pombe. This study reveals a dominant role of transcriptional regulation in response to stress, but also points to the first minutes after stress induction as a critical time when the coordinated control of mRNA turnover can support the control of transcription for rapid gene regulation. In addition, we uncover specialized gene expression strategies associated with distinct functional gene groups, such as simultaneous transcriptional repression and mRNA destabilization for genes encoding ribosomal proteins, delayed mRNA destabilization with varying contribution of transcription for ribosome biogenesis genes, dominant roles of mRNA stabilization for genes functioning in protein degradation, and adjustment of both transcription and mRNA turnover during the adaptation to stress. We also show that genes regulated independently of the bZIP transcription factor Atf1p are predominantly controlled by mRNA turnover, and identify putative cis-regulatory sequences that are associated with different gene expression strategies during the stress response. This study highlights the intricate and multi-faceted interplay between transcription and RNA turnover during the dynamic regulatory response to stress.
authors.affiliation: Department of Genetics, Evolution & Environment and UCL Cancer Institute; University College London; London, UK.
authors.forename: Samuel
authors.initials: S
authors.lastname: Marguerat
authors.affiliation: European Molecular Biology Laboratory; EMBL-EBI; Wellcome Trust Genome Campus; Hinxton, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Lawler
authors.affiliation: European Molecular Biology Laboratory; EMBL-EBI; Wellcome Trust Genome Campus; Hinxton, UK.
authors.forename: Alvis
authors.initials: A
authors.lastname: Brazma
authors.affiliation: Department of Genetics, Evolution & Environment and UCL Cancer Institute; University College London; London, UK.
authors.forename: Jürg
authors.initials: J
authors.lastname: Bähler
mesh_terms: D051697:Activating Transcription Factor 1 / Q000378:metabolism; D000220:Adaptation, Biological; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D008954:Models, Biological; D059372:Nucleotide Motifs; D018384:Oxidative Stress / Q000235:genetics*; D010750:Phosphoproteins / Q000378:metabolism; D056510:Position-Specific Scoring Matrices; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D038621:Regulatory Sequences, Ribonucleic Acid; D012269:Ribosomal Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D051697:Activating Transcription Factor 1; D010750:Phosphoproteins; D012333:RNA, Messenger; D038621:Regulatory Sequences, Ribonucleic Acid; D012269:Ribosomal Proteins; D029702:Schizosaccharomyces pombe Proteins; C106740:atf1 protein, S pombe
keywords: Atf1; RNA Polymerase II; fission yeast; gene regulation; mRNA turnover; mathematical modelling; oxidative stress; post-transcriptional control; ribosome biogenesis