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 (<i>Nicotiana benthamiana</i>), whereas knockout of <i>MC4</i> and knockdown of <i>La1</i> 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.