Novel roles of mono-ADP-ribosylation in interferon signalling and beyond

ADP-ribosylation (ADPr) is a post-translational modification best characterized in the context of DNA damage signalling, where PARP1 and PARP2 catalyse the formation of poly-ADPr chains. However, the roles of mono-ADPr, which is catalysed by most other members of the PARP family, are only recently beginning to emerge. Interestingly, most mono-ADPr transferases are induced by interferon (IFN) signalling, indicating that this modification plays important roles in innate immune responses. Indeed, several viruses, including coronaviruses and alphaviruses, encode hydrolases that remove mono-ADP-ribosylation catalysed by these host enzymes, and abrogation of viral hydrolase activity leads to severe viral attenuation. However, how host mono-ADPr contributes to antiviral responses is currently undetermined. Recently, we showed that PARP9, DTX3L and PARP14 promote IFN-induced mono-ADPr within an undefined cytosolic structure. We have now identified a number of additional factors that localize to this structure, which we propose to call ICAB, for “IFN-induced cytoplasmic ADPr body”. Here, we will dissect the functions of ICABs in the interferon response, and the molecular mechanisms that drive its biology. We will also explore the involvement of mono-ADPr in other aspects of the interferon response and in related signalling pathways. Keywords: post-translational modifications; innate immunity; ADP-ribosylation; interferon; PARP