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

Abstract

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.

Comparative dynamic transcriptome analysis (cDTA) reveals mutual feedback between mRNA synthesis and degradation

“…To test this, we conducted a corresponding heat-shock experiment on wild-type cells. We analyzed the total mRNA from this experiment together with the data from the rpb1-1 mutant by conventional decay time series analysis (Holstege et al 1998;Wang et al 2002;Grigull et al 2004;Shalem et al 2008). The obtained mRNA half-lives during heat shock correlated very well with data derived from the rpb1-1 mutant strain and with published half-lives obtained with this strain (Fig.…”

“…Transcription arrest has been achieved by adding the transcription inhibitor 1,10-phenanthroline (Dori-Bachash et al 2011) or by shifting the temperature-sensitive mutant strain rpb1-1, which carries point mutations in the largest subunit of Pol II (Nonet et al 1987), to the restrictive temperature (Holstege et al 1998;Wang et al 2002;Grigull et al 2004;Shalem et al 2008). To investigate whether the latter method yields reliable data or whether it perturbs mRNA metabolism, we regenerated the rpb1-1 strain and analyzed it with cDTA using published growth parameters (Holstege et al 1998) (Methods).…”

Metabolic cycling in single yeast cells from unsynchronized steady-state populations limited on glucose or phosphate

“…In addition, we prioritized our selections based on relatively high abundance of mRNAs according to several genome-wide studies using microarrays (17)(18)(19) or high-capacity sequencing (20). Where possible, we also favored genes whose mRNAs had been reported to have relatively short half-lives (Table S1).…”

Arabidopsis Deadenylases AtCAF1a and AtCAF1b Play Overlapping and Distinct Roles in Mediating Environmental Stress Responses

“…The steady-state level of messenger RNA (mRNA) within a cell is determined by the combination of the rate of transcription and the rate of posttranscriptional processes regulating mRNA decay. Genome-wide approaches are revealing that in response to environmental stimuli there is a large reprogramming of gene expression (Eulgem, 2005;Swindell, 2006;Kilian et al, 2007;Ma and Bohnert, 2007;Walley et al, 2007;Walther et al, 2007;Shalem et al, 2008). While changes in the rate of mRNA degradation provide a rapid mechanism to alter mRNA abundance, research has largely focused on changes in transcriptional regulation as a means to control mRNA levels (Gutierrez et al, 2002;Yamashita et al, 2005;Narsai et al, 2007;Belostotsky and Sieburth, 2009;Chiba and Green, 2009;Lee and Glaunsinger, 2009).…”