Nutrient status regulates MED19a phase separation for ORESARA1‐dependent senescence

Summary The mediator complex is highly conserved in eukgaryotes and is integral for transcriptional responses. Mediator subunits associate with signal‐responsive transcription factors (TF) to activate expression of specific signal‐responsive genes. As the key TF of Arabidopsis thaliana senescence, ORESARA1 (ORE1) is required for nitrogen deficiency (−N) induced senescence; however, the mediator subunit that associates with ORE1 remains unknown. Here, we show that Arabidopsis MED19a associates with ORE1 to activate −N senescence‐responsive genes. Disordered MED19a forms inducible nuclear condensates under −N that is regulated by decreasing MED19a lysine acetylation. MED19a carboxyl terminus (cMED19a) harbors a mixed‐charged intrinsically disordered region (MC‐IDR) required for ORE1 interaction and liquid–liquid phase separation (LLPS). Plant and human cMED19 are sufficient to form heterotypic condensates with ORE1. Human cMED19 MC‐IDR, but not yeast cMED19 IDR, partially complements med19a suggesting functional conservation in evolutionarily distant eukaryotes. Phylogenetic analysis of eukaryotic cMED19 revealed that the MC‐IDR could arise through convergent evolution. Our result of MED19 MC‐IDR suggests that plant MED19 is regulated by phase separation during stress responses.