A virus-encoded protein suppresses methylation of the viral genome in the Cajal body through its interaction with AGO4

ABSTRACT In plants, establishment of de novo DNA methylation is regulated by the RNA-directed DNA methylation (RdDM) pathway. RdDM machinery is known to concentrate in the Cajal body, but the biological significance of this localization has remained elusive. Here, we show that the anti-viral methylation of the Tomato yellow leaf curl virus (TYLCV) genome occurs specifically in the Cajal body of Nicotiana benthamiana cells. Methylation of the viral genome is countered by a virus-encoded protein, V2, which interacts with the central RdDM component AGO4, interfering with its binding to the viral DNA; Cajal body localization of the V2-AGO4 interaction is required for the viral protein to exert this function. Taken together, our results draw a long sought-after functional connection between RdDM, the Cajal body, and anti-viral DNA methylation, paving the way for a deeper understanding of DNA methylation and anti-viral defences in plants.