Plastidial metabolite MEcPP induces a transcriptionally centered stress-response hub via the transcription factor CAMTA3
Plastidial metabolite MEcPP induces a transcriptionally centered stress-response hub via the transcription factor CAMTA3
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DOI：
10.1073/pnas.1602582113
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发表时间：
2016-08-02
影响因子：
11.1
通讯作者：
Dehesh, Katayoon
中科院分区：
文献类型：
--
作者：
Benn, Geoffrey;Bjornson, Marta;Dehesh, Katayoon
一般应激反应（GSR）是一种进化上保守的快速、短暂的基因转录重编程，其核心是将环境信号转变成细胞反应，导致代谢和生理调整以应对普遍条件。定义 GSR 的调节组件将为了解早期应激反应模块的设计原理及其在协调适应性反应的主调节器中的作用提供重要的见解。甲基赤藓醇环二磷酸（MEcPP）是一种双功能化学实体，既作为质体甲基赤藓醇磷酸（MEP）途径产生的类异戊二烯的前体，又作为胁迫特异性逆行信号，在ceh1（组成型表达氢过氧化物裂解酶1）突变植物中过度积累，导致大规模转录改变。对ceh1植物中微阵列数据的生物信息学分析表明，在强诱导基因的启动子中，胁迫响应顺式元件和关键GSR标记——快速胁迫响应元件（RSRE）的过度表达。 ceh1 植物携带已建立的 4xRSRE：荧光素酶报告基因，用于监测 GSR 支持在此突变背景中反应的组成型激活。遗传学和药理学方法证实了 MEcPP 通过转录因子钙调蛋白结合转录激活剂 3 (CAMTA3) 以钙依赖性方式诱导 RSRE 的特异性。此外，IRE1a（肌醇需要蛋白1）和bZIP60（碱性亮氨酸拉链60）的CAMTA3依赖性激活，这两个含有未折叠蛋白反应基因的RSRE，将MEcPP介导的GSR诱导与内质网中蛋白折叠稳态的增强联系起来。这些发现引入了关键质体逆行信号代谢物诱导核 GSR 进行转录调节的概念，从而为了解细胞器间通讯在塑造细胞适应性反应中的作用提供了一个窗口。
The general stress response (GSR) is an evolutionarily conserved rapid and transient transcriptional reprograming of genes central for transducing environmental signals into cellular responses, leading to metabolic and physiological readjustments to cope with prevailing conditions. Defining the regulatory components of the GSR will provide crucial insight into the design principles of early stress-response modules and their role in orchestrating master regulators of adaptive responses. Overaccumulation of methylerythritol cyclodiphosphate (MEcPP), a bifunctional chemical entity serving as both a precursor of isoprenoids produced by the plastidial methylerythritol phosphate (MEP) pathway and a stress-specific retrograde signal, in ceh1 (constitutively expressing hydroperoxide lyase1)-mutant plants leads to large-scale transcriptional alterations. Bioinformatic analyses of microarray data in ceh1 plants established the over-representation of a stress-responsive cis element and key GSR marker, the rapid stress response element (RSRE), in the promoters of robustly induced genes. ceh1 plants carrying an established 4xRSRE: Luciferase reporter for monitoring the GSR support constitutive activation of the response in this mutant background. Genetics and pharmacological approaches confirmed the specificity of MEcPP in RSRE induction via the transcription factor CALMODULIN-BINDING TRANSCRIPTION ACTIVATOR 3 (CAMTA3), in a calcium-dependent manner. Moreover, CAMTA3-dependent activation of IRE1a (inositol-requiring protein-1) and bZIP60 (basic leucine zipper 60), two RSRE containing unfolded protein-response genes, bridges MEcPP-mediated GSR induction to the potentiation of protein-folding homeostasis in the endoplasmic reticulum. These findings introduce the notion of transcriptional regulation by a key plastidial retrograde signaling metabolite that induces nuclear GSR, thereby offering a window into the role of interorgannellar communication in shaping cellular adaptive responses.