Squair et al. show that ZNFX1 restricts ssRNA virus replication by integrating SF1 helicase activity with dual E3 ligase mechanisms. ATP-dependent RNA binding activates E3 function, driving self-propagating aggregation and RNA sequestration. Deubiquitination reverses this process, enabling aggregate disassembly and RNA release, positioning ZNFX1 as a stress-responsive RNA buffer.