Figure 7

Model for the generation and action of HIV-1 TAR derived miRNA. Basal transcription of the HIV-1 LTR produces short RNA transcripts containing the TAR element. These RNA elements are directed to the cytoplasm where they are processed by Dicer to yield a viral miRNA. This viral miRNA associates with the RISC or RITS complex and through homology to sequence contained in the viral RNA, as well as the proviral genome, may direct silencing of viral gene expression. Alternatively, the viral miRNA may contain sufficient homology to mediate silencing of cellular genes. Our work identifies a role for Dicer in the generation of an HIV-1 miRNA, but we cannot rule out the involvement of Drosha in vivo. An alternate pathway for the generation of this miRNA is indicated by the dashed arrows. It should be noted that the two pathways may generate miRNA with slightly different sequence, as cleavage by the Drosha enzyme would eliminate some sequence from the base of the stem.