Being sessile, plants have evolved complex and intricate response networks to biotic and abiotic stresses. Identification of the signaling hub(s) that activates universal components of these stress responses has been a challenge. Recently, we identified a novel retrograde stress-sensor methylerythritol cyclodiphosphate (MEcPP), previously known solely as an intermediate in the isoprenoid biosynthetic pathway, as a stress sensor that communicates environmental perturbations sensed by plastids back to the nucleus. MEcPP specifically coordinates expression of key stress-responsive nuclear genes. We identified RSRE (Rapid Stress Response Element) as a general stress inducible cis-regulatory element in stress responsive promoters. In addition, combinatorial transcriptome and proteome profiling studies revealed that MEcPP increases transcript and protein levels for a sub-set of the core unfolded protein response (UPR) genes. As such, our findings provide a link between a single retrograde signaling molecule and its targeted ensemble of endoplasmic reticulum (ER) genes to induce UPR components prior to the accumulation of misfolded proteins.