Targeted MYC2 stabilization confers citrus Huanglongbing resistance

Abstract

Huanglongbing (HLB) is a devastating citrus disease. In this work, we report an HLB resistance regulatory circuit in <i>Citrus</i> composed of an E3 ubiquitin ligase, PUB21, and its substrate, the MYC2 transcription factor, which regulates jasmonate-mediated defense responses. A helitron insertion in the <i>PUB21</i> promoter introduced multiple MYC2-binding cis-elements to create a regulatory circuit linking the PUB21 activity with MYC2 degradation. Ectopic expression of a natural dominant-negative <i>PUB21</i> paralog discovered in distant <i>Citrus</i> relatives stabilized MYC2 and conferred resistance to HLB. Antiproteolysis peptides (APPs), identified by artificial intelligence, stabilized MYC2 by binding and inhibiting PUB21 activity. A 14-amino acid peptide, APP3-14, molecularly controlled HLB in greenhouse and field trials. This approach represents a strategy to combat uncultivable pathogens through targeted disease resistance protein stabilization.