| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3428096 | Virus Research | 2016 | 8 Pages |
•Viral-derived long non-coding RNAs (sfRNAs) are made in all Flaviviridae infections.•The host exonuclease Xrn1 stalls on viral RNA structures to produce these lncRNAs.•Stalled Xrn1 is also repressed, leading to dysregulation of cellular mRNA stability.•sfRNA serves as a decoy to counteract aspects of the interferon and RNAi pathways.•Flaviviral lncRNAs play a key role in replication, cytopathology and pathogenesis.
Members of the Flaviviridae (e.g., Dengue virus, West Nile virus, and Hepatitis C virus) contain a positive-sense RNA genome that encodes a large polyprotein. It is now also clear most if not all of these viruses also produce an abundant subgenomic long non-coding RNA. These non-coding RNAs, which are called subgenomic flavivirus RNAs (sfRNAs) or Xrn1-resistant RNAs (xrRNAs), are stable decay intermediates generated from the viral genomic RNA through the stalling of the cellular exoribonuclease Xrn1 at highly structured regions. Several functions of these flavivirus long non-coding RNAs have been revealed in recent years. The generation of these sfRNAs/xrRNAs from viral transcripts results in the repression of Xrn1 and the dysregulation of cellular mRNA stability. The abundant sfRNAs also serve directly as a decoy for important cellular protein regulators of the interferon and RNA interference antiviral pathways. Thus the generation of long non-coding RNAs from flaviviruses, hepaciviruses and pestiviruses likely disrupts aspects of innate immunity and may directly contribute to viral replication, cytopathology and pathogenesis.
