Noncanonical cytoplasmic processing of viral microRNAs

Jillian S. Shapiro, Andrew Varble, Alissa M. Pham, Benjamin R. Tenoever

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2068-2074
Number of pages7
JournalRNA
Volume16
Issue number11
DOIs
StatePublished - Nov 2010

Keywords

  • Antiviral vector
  • RNA interference
  • Synthetic biology
  • Viral engineering
  • siRNA delivery

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