Potyviruses recruit host eIF4A3 to block m6A-mediated RNA decay by steric hindrance of viral RNA methylation in plants

Abstract N 6-methyladenosine (m6A), a critical epitranscriptomic modification, regulates RNA metabolism and antiviral defenses. However, how pathogens evade m6A-mediated RNA decay in plants remains poorly understood. Here, we uncover a dynamic m6A modification arms race during infection of sugarcane mosaic virus (SCMV), a prevalent potyvirus that infects maize and causes 20%–80% yield loss. We demonstrate that maize m6A methyltransferase (ZmMTA) specifically deposits m6A at A6556 of the SCMV genomic RNA, enabling recognition by the m6A reader EVOLUTIONARILY CONSERVED C-TERMINAL REGION 23 (ZmECT23). ZmECT23 directly recruits the ZmCCR4-NOT (carbon catabolite repressor 4–negative on TATA) complex to facilitate viral RNA decay. Strikingly, SCMV counters the defense via its nuclear inclusion protein a protease (NIa-Pro), which hijacks maize eukaryotic initiation factor 4A-III (ZmeIF4A3) into viral replication complexes. ZmeIF4A3 sterically blocks ZmMTA-mediated m6A deposition, thereby preventing viral RNA from degradation. Mechanistic conservation is observed in potato virus Y and turnip mosaic virus, two other potyviruses that are modified with m6A. Our study identifies eIF4A3 as a key m6A regulator in plants and reveals a strategy used by potyviruses to subvert m6A-based immunity via exploiting host RNA helicases. These findings provide mechanistic insights into host-pathogen interactions as mediated by m6A and suggest eIF4A3 as a potential target for engineering m6A-based antiviral crops.