Marguerat Samuel, Lawler Katherine, Brazma Alvis, Bähler Jürg
Department of Genetics, Evolution & Environment and UCL Cancer Institute; University College London; London, UK.
European Molecular Biology Laboratory; EMBL-EBI; Wellcome Trust Genome Campus; Hinxton, UK.
RNA Biol. 2014;11(6):702-14. doi: 10.4161/rna.29196. Epub 2014 Jul 9.
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.
转录水平和转录后水平的调控协同作用以塑造基因调控,目前我们对此仅了解一部分。在此,我们表明,结合两种简单且非侵入性的基因组技术,并运用动力学数学建模,能够深入了解粟酒裂殖酵母在氧化应激反应中RNA调控的复杂动态。这项研究揭示了转录调控在应激反应中的主导作用,但也指出应激诱导后的最初几分钟是一个关键时期,此时mRNA周转的协同控制能够支持转录控制以实现快速基因调控。此外,我们发现了与不同功能基因组相关的专门基因表达策略,例如编码核糖体蛋白的基因同时存在转录抑制和mRNA去稳定化,核糖体生物发生基因的mRNA去稳定化延迟且转录贡献各异,在蛋白质降解中起作用的基因以mRNA稳定化为主导,以及在适应应激过程中转录和mRNA周转都进行了调整。我们还表明,独立于bZIP转录因子Atf1p调控的基因主要受mRNA周转控制,并鉴定出在应激反应期间与不同基因表达策略相关的假定顺式调控序列。这项研究突出了在应激动态调控反应过程中转录与RNA周转之间复杂且多方面的相互作用。