Plastidial metabolite MEcPP induces a transcriptionally centered stress-response hub via the transcription factor CAMTA3

Abstract

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 stressresponse 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 overrepresentation 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 4×RSRE: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.S tress-triggered transcriptional reprogramming plays fundamental roles in transducing stress signals and ultimately enabling adaptive responses through readjustments of the appropriate physiological and metabolic processes. The initial transcriptional reprograming known as the "general stress response" (GSR), at times referred to as the "cellular stress response" or "core stress response," is a recognized evolutionarily conserved stress response present across kingdoms (1-5).The GSR, a rapid and transient transcriptional reprogramming, is induced by a wide variety of stresses imposed upon organisms by environmental forces on macromolecules such as membrane lipids, proteins, and/or DNA (6). Bioinformatic analysis of the promoters of the rapid wound-response genes (5 min after mechanical damage) in plants led to the identification of an overrepresented functional cis-element, the rapid stress response element (RSRE), which is analogous to the yeast stress response element (STRE) (4, 7). A reporter line containing luciferase (LUC) driven by a synthet...

Shedding light on the methylerythritol phosphate (MEP)‐pathway: long hypocotyl 5 (HY5)/phytochrome‐interacting factors (PIFs) transcription factors modulating key limiting steps

“…The MEP pathway is a key biosynthetic route responsible for the synthesis of essential compounds and signals that modulate developmental and stress responses (Bouvier et al, 2005;Umehara et al, 2008;Hemmerlin et al, 2012;Walley et al, 2015;Benn et al, 2016). Also, several of the MEP pathway products have importance for human health and nutrition.…”

Chloroplast-to-Nucleus Signaling Regulates MicroRNA Biogenesis in Arabidopsis

“…Reactive oxygen species (ROS), formed during photosynthesis (Leister, 2017) or redox-dependent signaling, reprograms cellular transcriptome by upregulating a series of transcription factors (Br€ autigam et al, 2009;Sewelam et al, 2014). The transcription factor CAMTA4 mediates transcriptional activation of a stress-responsive cis element by methylerythritol cyclodiphosphate (MEcPP), a signaling molecule from the isoprenoid biosynthetic pathway (Benn et al, 2016;Xiao et al, 2012), whereas the transcription factor ABI4 has been identified as a critical hub that links multiple retrograde signals to transcriptional regulation of nuclear gene expression (Koussevitzky et al, 2007). Some transcription factors, such as PTM (Sun et al, 2011) and Whirly transcription factors (Foyer et al, 2014), can act as retrograde signals themselves and, upon translocation to the nucleus, directly regulate gene transcription.…”

Transcriptome Analysis Shows Activation of Stress and Defense Responses by Silencing of Chlorophyll Biosynthetic Enzyme CHLI in Transgenic Tobacco

“…In the comparative analysis of RNA-seq data from two chlorosis models, we also found that GO terms of “ERAD pathways” and “response to ER stress” were specifically enriched in i-hpHSP90C plants ( Supplementary Figure S5A,B ). A retrograde signal molecule, methylerythritol cyclodiphosphate, and SA reportedly activate the unfolded protein response (UPR) [ 37 , 38 , 39 , 40 ]. However, the role of UPR pathway in chlorosis development remains to be studied.…”