Figure 1

Viral suppressors of the mammalian RNA silencing pathway. The diagram shows the pathway of RNA silencing mediated by miRNAs and siRNAs. miRNA genes are transcribed as long transcripts in the nucleus, usually by RNA polymerase II. These long transcripts (pri-mRNAs) with local stem-loop structure are recognized and processed into miRNA precursors (pre-miRNAs) of approximately 70 nucleotides by the Microprocessor complex containing Drosha and Pasha. The highly structured pre-miRNAs are then exported into the cytoplasm by exportin-5. In the cytoplasm, pre-miRNAs are recognized and further processed into approximately 22-nucleotide mature miRNA duplexes by the Dicer-TRBP complex. Dicer also generates approximately 22-nucleotide siRNA duplexes from long dsRNAs. The miRNA or siRNA duplex is unwound during the assembly of the RNA-induced silencing complex (RISC) and only one strand is loaded while the other is degraded. The miRNA or siRNA in the RISC finds and silences its target mRNAs through sequence-specific recognition. The viral products that interfere with the pathway are shown, and the points at which they possibly act on the pathway to inhibit RNA silencing are indicated by barred lines. NS1, E3L, B2, and Tat are viral proteins (see text); VA1 is a noncoding adenoviral RNA.