%0 Journal Article
%T PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation.
%A Kar P
%A Chatrin C
%A Đukić N
%A Suyari O
%A Schuller M
%A Zhu K
%A Prokhorova E
%A Bigot N
%A Ahel J
%A Elsborg JD
%A Nielsen ML
%A Clausen T
%A Huet S
%A Niepel M
%A Sanyal S
%A Ahel D
%A Smith R
%A Ahel I
%J EMBO J
%V 43
%N 14
%D 2024 Jul 4
%M 38834853
%F 14.012
%R 10.1038/s44318-024-00126-0
%X PARP-catalysed ADP-ribosylation (ADPr) is important in regulating various cellular pathways. Until recently, PARP-dependent mono-ADP-ribosylation has been poorly understood due to the lack of sensitive detection methods. Here, we utilised an improved antibody to detect mono-ADP-ribosylation. We visualised endogenous interferon (IFN)-induced ADP-ribosylation and show that PARP14 is a major enzyme responsible for this modification. Fittingly, this signalling is reversed by the macrodomain from SARS-CoV-2 (Mac1), providing a possible mechanism by which Mac1 counteracts the activity of antiviral PARPs. Our data also elucidate a major role of PARP9 and its binding partner, the E3 ubiquitin ligase DTX3L, in regulating PARP14 activity through protein-protein interactions and by the hydrolytic activity of PARP9 macrodomain 1. Finally, we also present the first visualisation of ADPr-dependent ubiquitylation in the IFN response. These approaches should further advance our understanding of IFN-induced ADPr and ubiquitin signalling processes and could shed light on how different pathogens avoid such defence pathways.