PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation

Journal article

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.

Authors: Kar, P; Chatrin, C; Đukić, N; Suyari, O; Schuller, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: EMBO Press
• Journal: The EMBO Journal
• Volume: 43
• Issue: 14
• Pages: 2929-2953
• Publication date: 2024-06-04
• Acceptance date: 2024-05-08
• DOI: 10.1038/s44318-024-00126-0
• EISSN: 1460-2075
• Language: English
• Keywords: SARS-CoV2; Immune Response; Interferon Response; ADP-ribosylation; Ubiquitin