Fig 1.
The concept of “triphosphate RNA balance”.
Experiments with DUSP11 demonstrate that increasing or decreasing the cellular pool of 5′-PPP RNA modulates the sensitivity of the cell to activating the antiviral response. This argues that balancing the 5′-PPP RNA pool is essential for both preventing autoinflammation and initiating a timely and effective antiviral response. DUSP, dual-specificity phosphatase; 5′-PPP, 5′-triphosphate.
Fig 2.
DUSP11 acts on host and viral 5′-triphosphate RNAs reducing their ability to stimulate an antiviral response.
DUSP11 acts on RNAP III transcripts, possibly co-transcriptionally in the nucleus and upon delivery via extracellular vesicles (EV) in the cytosol, to prevent an inappropriate inflammatory response. Experimentally reducing DUSP11 leads to enhanced RIG-I signaling. Equally important is that increasing DUSP11 leads to attenuated RIG-I signaling and enhanced virus infection. RNA viruses may have evolved to allow their transcripts access to DUSP11 to reduce their visibility to host pathogen recognition receptors. DUSP, dual-specificity phosphatase; EV, extracellular vesicle; RNAP III, RNA polymerase III; RBP, RNA binding protein.