Activation of stress-response genes by retrograde signaling-mediated destabilization of nuclear importin IMPα-9 and its interactor TPR2

Deciphering stress-induced retrograde signal transmission from plastids to the nucleus has long puzzled plant biologists. To address this, we performed a suppressor screen of the ceh1 mutant, known for elevated MEcPP levels, and identified the gain-of-function mutant impα-9, which reverses dwarfism and suppresses stress-response genes in the ceh1 background despite heightened MEcPP.Subsequent genetics and biochemical analyses established that the accumulation of MEcPP initiates an upsurge in ASK1 abundance, a pivotal component in the proteasome degradation pathway. This increase in ASK1 prompts the degradation of IMPα-9. Additionally, we uncovered a protein interaction between IMPα-9 and TPR2, a transcriptional co-suppressor. Reduction in IMPα-9 levels coincides with a decrease in TPR2 abundance. Significantly, these interactions were disrupted in impα-9 mutants, highlighting the critical role of a single amino acid alteration in maintaining these associations. Disruption of these interactions results in the reversal of MEcPP-associated phenotypes.ChIP-seq analyses unveiled TPR2's binding to stress response genes and suggested IMPα-9-DNA association. Together, these associations function to suppress stress genes under normal conditions, but this suppression is alleviated in response to stress through the degradation of the suppressing machinery. The biological relevance of these findings was emphasized during high light stress, characterized by MEcPP accumulation, elevated ASK1 levels, degradation of IMPα-9, reduced TPR2 abundance, and subsequent activation of a network of stress response genes.In essence, our study uncovers new insights into plant adaptive responses, revealing complex interactions among retrograde signaling, the proteasome, and nuclear transport machinery, and establishes plastids as a regulatory stress response hub.