Contributions of transcription and mRNA decay to gene expression dynamics of fission yeast in response to oxidative stress

• Published in: RNA biology Vol. 11; no. 6; pp. 702 - 714
• Main Authors: Marguerat, Samuel, Lawler, Katherine, Brazma, Alvis, Bähler, Jürg
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01-06-2014; Landes Bioscience
• Subjects: Activating Transcription Factor 1 - metabolism; Adaptation, Biological; Atf1; Cluster Analysis; fission yeast; Gene Expression Profiling; Gene Expression Regulation, Fungal; gene regulation; mathematical modeling; Models, Biological; mRNA turnover; Nucleotide Motifs; oxidative stress; Oxidative Stress - genetics; Phosphoproteins - metabolism; Position-Specific Scoring Matrices; post-transcriptional control; Regulatory Sequences, Ribonucleic Acid; Research Paper; Ribosomal Proteins - metabolism; ribosome biogenesis; RNA Polymerase II; RNA Stability; RNA, Messenger - genetics; RNA, Messenger - metabolism; Schizosaccharomyces - genetics; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe Proteins - metabolism; Transcription, Genetic; Transcriptome; Atf1; post-transcriptional control; mathematical modelling; gene regulation; mRNA turnover; fission yeast; RNA Polymerase II; oxidative stress; ribosome biogenesis
• ISSN: 1547-6286; 1555-8584
• DOI: 10.4161/rna.29196

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, affords 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.