It's Complicated: The Pro- and Antiviral Functions of RNA Condensation

Eukaryotic cells compartmentalize critical biomolecular processes within membrane-bound organelles. Within these organelles, nucleic acids and proteins further compartmentalize into distinct structures known as membraneless organelles (MOs) via liquid-liquid phase separation. MOs enhance the specificity and rate of molecular processes by concentrating specific substrates, and their ability to quickly assemble and disassemble enables rapid regulation of molecular processes. RNA contributes to MO assembly and maintenance due to its ability to form a network of weak trans-molecular RNA-RNA interactions and multivalent RNA-protein interactions. Unsurprisingly, viruses have taken advantage of RNA condensation to enhance their replication and evade detection by host cells. However, recent studies have shown that several cellular antiviral sensors specifically activate on condensed viral RNAs. In this review, we discuss the intricate role of RNA condensation in viral replication and innate immune sensing and how host cells and viruses modulate these processes.