Regulated resource re-allocation is transcriptionally hard wired into the yeast stress response

Many organisms maintain generalized stress responses activated by adverse conditions. Although details vary, a common theme is the redirection of transcriptional and translational capacity away from growth-promoting genes and toward defense genes. Yet the precise roles of these coupled programs are difficult to dissect. Here we investigated Saccharomyces cerevisiae responding to salt as a model stressor. We used molecular, genomic, and single-cell microfluidic methods to examine the interplay between transcription factors Msn2 and Msn4 that induce stress-defense genes and Dot6 and Tod6 that transiently repress growth-promoting genes during stress. Surprisingly, loss of Dot6/Tod6 led to slower acclimation to salt, whereas loss of Msn2/4 produced faster growth during stress. This supports a model where transient repression of growth-promoting genes accelerates the Msn2/4 response, which is essential for acquisition of subsequent peroxide tolerance. Remarkably, we find that Msn2/4 regulate DOT6 transcription, influence Dot6 activation dynamics, and are required for full repression of growth-promoting genes. Thus, Msn2/4 directly regulate the resource re-allocation needed to mount their own response. We discuss broader implications for common stress responses across organisms.诸多生物均会维持由不良环境条件激活的广谱应激响应。尽管具体细节存在差异，但其核心共性在于将转录与翻译资源从促生长基因向防御基因进行重分配。然而，上述协同调控程序的确切功能仍难以解析。本研究以酿酒酵母（Saccharomyces cerevisiae）为模式生物，探究其应对盐胁迫的应激响应机制。我们运用分子生物学、基因组学与单细胞微流控技术，解析了诱导应激防御基因的转录因子Msn2与Msn4，以及应激过程中瞬时抑制促生长基因的Dot6与Tod6之间的相互调控网络。令人意外的是，敲除Dot6/Tod6会延缓酵母对盐胁迫的适应进程，而敲除Msn2/4则可提升酵母在应激期间的生长速率。该结果支持如下模型：促生长基因的瞬时抑制能够加速Msn2/4的响应通路，而这一过程对于酵母获得后续过氧化物耐受性至关重要。值得注意的是，本研究发现Msn2/4可调控DOT6的转录过程，影响Dot6的激活动力学，且是完全抑制促生长基因的必要条件。由此可见，Msn2/4可直接调控启动自身应激响应所需的资源重分配过程。本研究还探讨了该发现对跨生物界广谱应激响应的普遍启示意义。