ENHANCED DISEASE RESISTANCE 1 (EDR1) is a negative regulator of powdery mildew resistance, cell death and ethylene-induced senescence. To identify components involved in EDR1 signaling, we performed a forward genetic screen for edr1 suppressors. In this screen, we identified the hpr1-4 mutation, which partially suppresses edr1-mediated resistance to the powdery mildew pathogen Golovinomyces cichoracearum and to mildew-induced cell death. However, the hpr1-4 mutation enhanced the ethylene-induced senescence phenotype of edr1. The hpr1-4 single mutant displayed enhanced susceptibility to the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 and to the oomycete pathogen Hyaloperonospora arabidopsidis Noco2. Arabidopsis HPR1 encodes a homologue of human HPR1, a component of the conserved THO/TREX complex that is required for mRNA export in yeast and human. HPR1 is expressed in various organs and throughout all developmental stages. HPR1 localizes in the nucleus, and significantly, mRNA export is compromised in the hpr1-4 mutant. Taken together, these data demonstrated that HPR1 plays an important role in disease resistance in plants and that the THO/TREX complex is functionally conserved among plants, yeast and humans. Our data indicates a general link between mRNA export, defense responses and ethylene signaling in plants.