ZNFX1, an immunoregulatory RNA helicase and E3 ubiquitin ligase, assembles into pleiomorphic polymers.

ZNFX1 forms pleiomorphic polymers that enhance immune signaling by coupling RNA sensing with ubiquitin signaling.

• Why it matters: Understanding ZNFX1's mechanisms is crucial because mutations cause recurrent infections, yet its functional regulation and structure remain unclear.
• What they did: Researchers used cryo-EM to determine structures of RNA-bound and RNA-free ZNFX1, revealing auto-inhibition of ATPase activity and its role as a bi-catalytic E3 ubiquitin ligase with unique domains.
• The result: The study shows ZNFX1 assembles into higher-order polymers that promote trans-auto-ubiquitylation, providing insights into its stability, antiviral activity, and potential for signal amplification in immunity.