The MC4-La1 cleavage module restricts plant virus infection by integrating R-motif–mediated defense mRNA translation

The plant cysteine protease metacaspases are structural homologs of animal caspases and play pivotal roles under biotic and abiotic stresses. However, whether metacaspases and purine-rich element (R-motif)–mediated defense messenger RNA translation are involved in plant antiviral immunity remains elusive. Here, we report that barley stripe mosaic virus (BSMV) infection activates metacaspase 4 (MC4) to cleave the RNA binding protein lupus autoantigen 1 (La1) behind residue arginine-448. The cleaved La1_1-448 version relocates to the cytoplasm and promotes the R-motif–mediated cap-independent defense mRNA translation. Moreover, MC4 overexpression restricts BSMV infection in tobacco (Nicotiana benthamiana), whereas knockout of MC4 and knockdown of La1 are more susceptible to diverse plant virus infection. To counteract plant defense, the BSMV γb protein directly interacts with and inhibits the self-processing of MC4 and subsequent La1 cleavage, thereby impairing La1-mediated immune responses. Collectively, our findings unveil a hitherto unknown defense mechanism whereby the MC4-La1 cleavage module inhibits virus infection by coordinating R-motif–mediated defense mRNA translation.