Noncanonical cytoplasmic processing of viral microRNAs.
Cellular utilization of RNA interference (RNAi) as a mechanism to combat virus infection is thought to be restricted to plants and invertebrates. In vertebrates, antiviral defenses are largely dependent on interferons (IFNs), with the use of small RNAs restricted to microRNA (miRNA)-mediated targeting of host transcripts. Here we demonstrate that incorporation of a primary miRNA into a cytoplasmic virus results in the formation of a Dicer-dependent, DGCR8-independent, mature miRNA capable of conferring RNAi-like activity. Processing of the viral mirtron-like product (virtron) is indistinguishable from endogenous miRNA maturation and elicits post-transcriptional gene silencing, albeit at a reduced level. Furthermore, virtrons impose Dicer-dependent, microprocessor-independent, and IFN-independent interference on virus replication in a sequence-specific manner. Taken together, these results suggest the existence of a noncanonical, small-RNA-based activity capable of processing cytoplasmic hairpins and perhaps contributing to the cell's antiviral arsenal.
Shapiro
Jillian S
JS
Microbiology Graduate School Training Program, Mount Sinai School of Medicine, New York, New York 10029, USA.
Varble
Andrew
A
Pham
Alissa M
AM
Tenoever
Benjamin R
BR
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003593:Cytoplasm / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000172:deficiency / Q000378:metabolism; D004722:Endoribonucleases / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D043244:Ribonuclease III; D012845:Sindbis Virus / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
D035683:MicroRNAs; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases