Hepatitis C virus (HCV) uses a human liver-specific microRNA called miR-122 for efficient viral RNA accumulation. We’ve always thought this was a quite unusual non-canonical interaction, since microRNAs usually downregulate gene expression, but miR-122 promotes HCV RNA accumulation. However, we are starting to think it may not be so unusual at all…

RNA is arguably the most versatile biological macromolecule owing to its ability to both encode genetic information and to fold back on itself to form complex 3D structures capable of highly-specific ligand recognition and catalysis. RNA structure is also dynamic, meaning that a structure that plays an important role in one biological state may not persist under different biological conditions. Studying RNA structure and organization is therefore crucial to understanding its biological function.

Flaviviruses have two proteins that participate in both replication organelle biogenesis and virion assembly, but their roles in either process aren’t entirely clear. How do flaviviruses, like Zika virus and dengue virus, build replication organelles? How do they assemble viral particles? We’re trying to figure that out.

While it has long been recognized that viruses form biomolecular condensates to mediate viral replication and virion assembly, the concept that this occurs through phase separation is relatively new. Consistent with this, the RNA virus proteome is enriched in features associated with phase separation, such as intrinsically disordered regions, low-complexity domains, and nucleic acid binding motifs. Accumulating evidence suggests that viruses are truly masters of phase separation.