CS-4-3 - Arabidopsis GCN2-eif2alpha Module Provides Novel Insights into the Integrated Stress Response Triggered by Reactive Oxygen Emanating from Chloroplasts

Cytosolic mRNA translation is subject to global and mRNA-specific regulation to balance energy and metabolic resources under dynamic environments. Central to these adjustments is a rapid-response regulatory switch comprised of the eukaryotic translation factor (eIF2)α and its only known kinase in plants, General Control Nonderepressible (GCN) 2. Together, the GCN2-eIF2α module represents an evolutionarily conserved homeostatic stress response program called the integrated stress response. What has remained unclear is the mechanism by which plants use the GCN2-eIF2α paradigm to regulate translation under different stresses? We provide evidence of a new signaling mechanism in Arabidopsis thaliana, where the GCN2-eIF2α paradigm extends the narrow definition of retrograde signaling by the chloroplast from transcriptional effects in the nucleus to the much quicker, translational regulation in the cytosol. Specifically, conditions that generate reactive oxygen species (ROS) in the chloroplast, such as excess light, cold, salt and herbicides, all rapidly activated GCN2, whereas mitochondrial and ER stress did not. In addition, GCN2 activity was mitigated by photosynthetic inhibitors and ROS quenchers. Interestingly, gcn2 knock-out seedlings were more sensitive to high light, cold and salt as compared to wild-type in a root elongation assay, supporting the notion that ROS associated signaling is mediated by the GCN2-eIF2α pathway. We describe here a genome-wide dataset on the translational defects in the gcn2 mutant. In the transcriptome of the gcn2 mutant responses to abiotic stress, and among them oxidative stress, as well as innate immune responses were sensitized. In keeping with a role for GCN2 in innate immunity, GCN2 kinase was also implicated in the priming by the fungal elicitor, chitin, an antibacterial defense response. In conclusion, we provide evidence that GCN2-eIF2α module is a missing link in a non-canonical retrograde signaling pathway whereby the status of the photosynthetic machinery feeds back to the cytosolic translation apparatus.

Coauthors: Ricardo Urquidi Camacho – University of Tennessee;Ju Guan – University of Tennessee;Philp Morgan – University of Tennessee;Albrecht von Arnim – University of Tennessee