IFN-Induced PARPs-Sensors of Foreign Nucleic Acids?

Cells have developed different strategies to cope with viral infections. Key to initiating a defense response against viruses is the ability to distinguish foreign molecules from their own. One central mechanism is the perception of foreign nucleic acids by host proteins which, in turn, initiate an efficient immune response. Nucleic acid sensing pattern recognition receptors have evolved, each targeting specific features to discriminate viral from host RNA. These are complemented by several RNA-binding proteins that assist in sensing of foreign RNAs. There is increasing evidence that the interferon-inducible ADP-ribosyltransferases (ARTs; PARP9-PARP15) contribute to immune defense and attenuation of viruses. However, their activation, subsequent targets, and precise mechanisms of interference with viruses and their propagation are still largely unknown. Best known for its antiviral activities and its role as RNA sensor is PARP13. In addition, PARP9 has been recently described as sensor for viral RNA. Here we will discuss recent findings suggesting that some PARPs function in antiviral innate immunity. We expand on these findings and integrate this information into a concept that outlines how the different PARPs might function as sensors of foreign RNA. We speculate about possible consequences of RNA binding with regard to the catalytic activities of PARPs, substrate specificity and signaling, which together result in antiviral activities.

Automated summary

Cells have developed various strategies to defend against viral infections, one of which is distinguishing foreign molecules from their own. This is achieved through the perception of foreign nucleic acids by host proteins, leading to an effective immune response. Pattern recognition receptors and RNA-binding proteins play crucial roles in sensing and distinguishing viral RNA from host RNA. Recent findings suggest that some ADP-ribosyltransferases (ARTs; PARP9-PARP15) contribute to immune defense and viral attenuation, but their activation, targets, and interference mechanisms are not well understood. One well-known RNA sensor, PARP13, has antiviral activities, and PARP9 has recently been described as a sensor for viral RNA.