Plant E3 ligases SNIPER1 and SNIPER2 broadly regulate the homeostasis of sensor NLR immune receptors

In both plants and animals, nucleotide-binding leucine-rich repeat (NLR) immune receptors perceive pathogen-derived molecules to trigger immunity. GlobalNLRhomeostasis must be tightly controlled to ensure sufficient and timely immune output while avoiding aberrant activation, the mechanisms of which are largely unclear. In a previous reverse genetic screen, we identified two novel E3 ligases,SNIPER1 and its homologSNIPER2, both of which broadly control the levels ofNLRimmune receptors inArabidopsis. Protein levels of sensorNLRs (sNLRs) are inversely correlated withSNIPER1 amount and the interactions betweenSNIPER1 andsNLRs seem to be through the common nucleotide-binding (NB) domains ofsNLRs. In support,SNIPER1 can ubiquitinate theNBdomains of multiplesNLRsin vitro. Our study thus reveals a novel process of global turnover ofsNLRs by two master E3 ligases for immediate attenuation of immune output to effectively avoid autoimmunity. Such unique mechanism can be utilized in the future for engineering broad-spectrum resistance in crops to fend off pathogens that damage our food supply.