Transient transcriptional responses to stress are generated by opposing effects of mRNA production and degradation

• Published in: Molecular systems biology 2008, Vol.4 (1), p.223-n/a
• Main Authors: Shalem, Ophir, Dahan, Orna, Levo, Michal, Martinez, Maria Rodriguez, Furman, Itay, Segal, Eran, Pilpel, Yitzhak
• Format: Article
• Language: English
• Subjects: Biodegradation; Career development planning; Datasets; Decay; Decay rate; Degradation; Deoxyribonucleic acid; DNA; DNA damage; EMBO09; EMBO36; Environmental changes; Gene expression; Gene Expression Regulation, Fungal - physiology; Genes; Genome, Fungal; Genomes; Kinetics; mRNA turnover; Oxidative stress; Production increases; Response time; RNA polymerase; RNA, Messenger - biosynthesis; RNA, Messenger - metabolism; Stress, Physiological - genetics; Transcription; Transcription, Genetic; Yeast; Yeasts
• ISSN: 1744-4292; 1744-4292
• DOI: 10.1038/msb.2008.59

The state of the transcriptome reflects a balance between mRNA production and degradation. Yet how these two regulatory arms interact in shaping the kinetics of the transcriptome in response to environmental changes is not known. We subjected yeast to two stresses, one that induces a fast and transient response, and another that triggers a slow enduring response. We then used microarrays following transcriptional arrest to measure genome‐wide decay profiles under each condition. We found condition‐specific changes in mRNA decay rates and coordination between mRNA production and degradation. In the transient response, most induced genes were surprisingly destabilized, whereas repressed genes were somewhat stabilized, exhibiting counteraction between production and degradation. This strategy can reconcile high steady‐state level with short response time among induced genes. In contrast, the stress that induces the slow response displays the more expected behavior, whereby most induced genes are stabilized, and repressed genes are destabilized. Our results show genome‐wide interplay between mRNA production and degradation, and that alternative modes of such interplay determine the kinetics of the transcriptome in response to stress. Synopsis The ability to follow genome‐wide changes in mRNA abundance over time, using microarray technology, has revolutionized the study of gene expression regulation. In a typical microarray experiment, cell samples are taken over a defined time course following a treatment, RNA is extracted and then hybridized to the microarrays to quantify the relative amount of each gene's mRNA at each sample. Such studies have revealed that in response to environmental stimuli the mRNA abundance of a large fraction of the genome changes either by increasing or decreasing its levels (Gasch et al , 2000 , 2001 ; Jelinsky et al , 2000 ; Gasch and Werner‐Washburne, 2002 ). In the study of transcriptional regulation, this data are often assumed to reflect transcriptional changes. Although this approach has greatly improved our understanding of transcriptional regulation, it does not address the fact that changes in mRNA abundance are influenced by both changes in transcription rates and mRNA stability. Not only that an increase or decrease in mRNA abundance can be achieved by both changes in production or degradation, different strategies of changing production and degradation rates will result in different kinetic behaviors of mRNA abundance ove