RNA silencing ͉ silencing suppressor ͉ cucumber mosaic virus ͉ Y-satellite P lants have three overlapping but distinct RNA silencing pathways that involve small interfering RNAs (siRNAs) and micro RNAs (miRNAs) (1). In the siRNA-related pathways, perfectly complementary dsRNAs are cleaved into siRNAs having two distinct size classes, 21-22 and 24 nt, by RNase III-type Dicer enzymes (2). These siRNAs are then incorporated into RNAinduced silencing complexes (RISCs) that guide the specific degradation of RNA in the cytoplasm (and possibly the nucleus) and͞or cytosine methylation of DNA in the nucleus (1, 3, 4). miRNAs are predominately 21-22 nt in length and are formed by the Dicer-mediated cleavage of hairpin-structured RNAs (5, 6). Both siRNAs and miRNAs play important roles in the control of spatial and temporal expression of key regulatory genes and can act through RISC-mediated mRNA cleavage (6, 7). The different pathways leading to the biogenesis of siRNAs and miRNAs in plants involve multiple protein factors that include the Dicer-like proteins (7, 8) and RNA-dependent RNA polymerases (9). A recent study has revealed that the 3Ј-terminal nucleotides of miRNAs in plants are methylated at their 2Ј or 3Ј hydroxyls by HEN1 (10), a protein previously shown to be required for the accumulation of miRNAs and sense transgene-derived siRNAs in Arabidopsis (11). It remains unclear, however, whether siRNAs are also methylated in plants, because HEN1 fails to methylate perfectly complementary duplex siRNAs in vitro (10).RNA silencing, and the siRNA pathway in particular, is a natural antiviral defense mechanism in plants (12). Consequently, many plant viruses encode proteins that can suppress RNA silencing by a variety of mechanisms. These silencing suppressors have become important tools in the elucidation of RNA silencing pathways in plants because they act differentially on the silencing machinery.