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

Pulak Kar; Chatrin Chatrin; Nina Đukić; Osamu Suyari; Marion Schuller; Kang Zhu; Evgeniia Prokhorova; Nicolas Bigot; Juraj Ahel; Jonas Damgaard Elsborg; Michael L Nielsen; Tim Clausen; Sébastien Huet; Mario Niepel; Sumana Sanyal; Dragana Ahel; Rebecca Smith; Ivan Ahel

doi:10.1038/s44318-024-00126-0

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

Pulak Kar, Chatrin Chatrin, Nina Đukić, Osamu Suyari, Marion Schuller, Kang Zhu, Evgeniia Prokhorova, Nicolas Bigot, Juraj Ahel, Jonas Damgaard Elsborg, Michael L Nielsen, Tim Clausen, Sébastien Huet, Mario Niepel, Sumana Sanyal, Dragana Ahel, Rebecca Smith^*, Ivan Ahel^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

23 Citationer (Scopus)

30 Downloads (Pure)

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.

Originalsprog	Engelsk
Tidsskrift	EMBO Journal
Vol/bind	43
Udgave nummer	14
Sider (fra-til)	2929-2953
ISSN	0261-4189
DOI	https://doi.org/10.1038/s44318-024-00126-0
Status	Udgivet - 2024

Bibliografisk note

Funding Information:
We would like to thank Ivan Matic for his kind gift of IgG- and HRP-conjugated anti-mono-ADPr antibodies. We thank the Soeding lab for generously providing public access to their MMSeqs2 prediction server. We also thank the Alan Wainman and the Dunn School Bioimaging Facility for expert advice and access to the microscope. We would like to thank Joey Riepsaame and the Genome Engineering Oxford (GEO) Facility for help making the DTX3L knockout cells. The work in Ivan Ahel\u2019s lab is supported by the following grants: Biotechnology and Biological Sciences Research Council (BB/R007195/1 and BB/W016613/1), Wellcome Trust (210634), Oxford University Challenge Seed Fund (USCF 456), Ovarian Cancer Research Alliance (813369). Ivan Ahel and Sumana Sanyal are jointly supported by Wellcome Trust (223107). The work in Dragana Ahel\u2019s lab is supported by the Edward Penley Abraham Research Fund. The Huet lab receives funding from the Agence Nationale de la Recherche (ANR-22-CE12-0039 AROSE), the Fondation ARC pour la recherche sur le cancer (ARCPJA2022060005190) and the Ligue Contre le Cancer (CD53).

Publisher Copyright:
© The Author(s) 2024.

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10.1038/s44318-024-00126-0Licens: CC BY

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Citationsformater

Kar, P., Chatrin, C., Đukić, N., Suyari, O., Schuller, M., Zhu, K., Prokhorova, E., Bigot, N., Ahel, J., Elsborg, J. D., Nielsen, M. L., Clausen, T., Huet, S., Niepel, M., Sanyal, S., Ahel, D., Smith, R., & Ahel, I. (2024). PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation. EMBO Journal, 43(14), 2929-2953. https://doi.org/10.1038/s44318-024-00126-0

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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.",

keywords = "ADP-ribosylation, Immune Response, Interferon Response, SARS-CoV2, Ubiquitin",

author = "Pulak Kar and Chatrin Chatrin and Nina {\D}uki{\'c} and Osamu Suyari and Marion Schuller and Kang Zhu and Evgeniia Prokhorova and Nicolas Bigot and Juraj Ahel and Elsborg, {Jonas Damgaard} and Nielsen, {Michael L} and Tim Clausen and S{\'e}bastien Huet and Mario Niepel and Sumana Sanyal and Dragana Ahel and Rebecca Smith and Ivan Ahel",

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doi = "10.1038/s44318-024-00126-0",

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T1 - PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation

AU - Kar, Pulak

AU - Chatrin, Chatrin

AU - Đukić, Nina

AU - Suyari, Osamu

AU - Schuller, Marion

AU - Zhu, Kang

AU - Prokhorova, Evgeniia

AU - Bigot, Nicolas

AU - Ahel, Juraj

AU - Elsborg, Jonas Damgaard

AU - Nielsen, Michael L

AU - Clausen, Tim

AU - Huet, Sébastien

AU - Niepel, Mario

AU - Sanyal, Sumana

AU - Ahel, Dragana

AU - Smith, Rebecca

AU - Ahel, Ivan

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - ADP-ribosylation

KW - Immune Response

KW - Interferon Response

KW - SARS-CoV2

KW - Ubiquitin

U2 - 10.1038/s44318-024-00126-0

DO - 10.1038/s44318-024-00126-0

M3 - Journal article

C2 - 38834853

AN - SCOPUS:85195164250

SN - 0261-4189

VL - 43

SP - 2929

EP - 2953

JO - EMBO Journal

JF - EMBO Journal

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