{Reference Type}: Journal Article
{Title}: PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation.
{Author}: Kar P;Chatrin C;Đukić N;Suyari O;Schuller M;Zhu K;Prokhorova E;Bigot N;Ahel J;Elsborg JD;Nielsen ML;Clausen T;Huet S;Niepel M;Sanyal S;Ahel D;Smith R;Ahel I;
{Journal}: EMBO J
{Volume}: 43
{Issue}: 14
{Year}: 2024 Jul 4
{Factor}: 14.012
{DOI}: 10.1038/s44318-024-00126-0
{Abstract}: 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.