The Geminiviral Effector AC4 Suppresses Nonsense-Mediated mRNA Decay Via Upf1 Degradation

RNA quality control pathways, particularly nonsense-mediated mRNA decay (NMD), function as critical antiviral defenses by degrading aberrant viral transcripts. However, how DNA geminiviruses counteract this RNA surveillance system remains largely unknown. Here we report that the Sri Lankan cassava mosaic virus (SLCMV) AC4 protein employs a novel strategy to suppress NMD: it targets the central regulator Upf1 for degradation. In Nicotiana benthamiana and Arabidopsis thaliana models, we demonstrate that SLCMV AC4 directly binds AtUpf1 via its N-terminal domain and triggers its depletion through the coordinated action of both the autophagy and ubiquitin-proteasome pathways. AC4 expression stabilized a broad range of endogenous NMD substrates and enhanced the accumulation and pathogenicity of a heterologous virus. Structural and functional analyses revealed that the N-terminal myristoylation motif of AC4 is indispensable for its function. While point mutations within this motif preserved Upf1 binding, they abrogated NMD suppression and Upf1 degradation, indicating the motif's essential role in assembling a functional degradation complex beyond mere interaction. Furthermore, we elucidate that AC4 activates autophagy by competitively disrupting the GAPC2-ATG3 interaction, thereby liberating ATG3 to promote autophagosome formation. Our findings unveil a sophisticated viral counter-defense mechanism in which a pathogen effector orchestrates the spatially coordinated degradation of a key host RNA surveillance factor, bridging the fields of plant-virus interactions, RNA biology, and host proteostasis.