uORF-mediated translation allows engineered plant disease resistance without fitness costs

Controlling plant disease has been a struggle for mankind since the advent of agriculture. Studies of plant immune mechanisms have led to strategies of engineering resistant crops through ectopic transcription of plants’ own defence genes, such as the master immune regulatory gene NPR1(1). However, enhanced resistance obtained through such strategies is often associated with significant penalties to fitness(2), making the resulting products undesirable for agricultural applications. To remedy this problem, we sought more stringent mechanisms of expressing defence proteins. Based on our latest finding that translation of key immune regulators, such as TBF1(3), is rapidly and transiently induced upon pathogen challenge (accompanying manuscript), we developed “TBF1-cassette” consisting of not only the immune-inducible promoter but also two pathogen-responsive upstream open reading frames (uORFs(TBF1)) of the TBF1 gene. We demonstrate that inclusion of the uORFs(TBF1)-mediated translational control over the production of snc1 (an autoactivated immune receptor) in Arabidopsis (At) and AtNPR1 in rice enables us to engineer broad-spectrum disease resistance without compromising plant fitness in the laboratory or in the field. This broadly applicable new strategy may lead to reduced use of pesticides and lightening of selective pressure for resistant pathogens.