Global changes in synthesis rates and mRNA stabilities during adaptive responses to cell wall stress in yeast

Eukaryotic cells respond to stress through complex transcriptional and post-transcriptional mechanisms. While various environmental stress responses are well studied in yeast, the effects of cell wall stress, primarily mediated by the Cell Wall Integrity (CWI) pathway, on mRNA dynamics remain less understood. This study employed the Genomic Run-On (GRO) method to analyse genome-wide changes in mRNA synthesis rates and stability in Saccharomyces cerevisiae exposed to Congo Red, a cell wall stress-inducing agent. We found a moderate global decrease in mRNA levels, mainly due to reduced synthesis rates, with overall mRNA stability largely unchanged. This contrasts with other stress conditions, where altered mRNA stability plays a prominent role. Additionally, Congo Red elicited a weaker activation of environmental stress response (ESR-up) genes than other stressors. However, cluster analysis revealed that about 15% of transcripts showed significant changes in stability, a novel finding for cell wall stress. Thus, many CWI-dependent genes showed mRNA accumulation resulting from both increased synthesis and enhanced stability. We also identified genes with increased synthesis but unchanged mRNA levels, revealing post-transcriptional buffering. Finally, we uncovered novel Congo Red-responsive genes and suggested that transcription factors Met32 and Rpn4, along with RNA-binding proteins Nab2 and Hrp1, may participate in the regulation of CWI-dependent genes. These findings advance our understanding of the transcriptional and post-transcriptional control of the cell wall stress response.