PARP14 is a PARP with Both ADP-ribosyl Transferase and Hydrolase Activities

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2023 Sep 13

PMID 37703374

Authors

Nina dukic

Oyvind Stromland

Jonas Damgaard Elsborg

Deeksha Munnur

Kang Zhu

Marion Schuller

Chatrin Chatrin

Pulak Kar

Lena Duma

Osamu Suyari

Johannes Gregor Matthias Rack

Domagoj Baretic

Dorian Richard Kenneth Crudgington

Josephine Groslambert

Gerissa Fowler

Sven Wijngaarden

Evgeniia Prokhorova

Jan Rehwinkel

Herwig Schuler

Dmitri V Filippov

Sumana Sanyal

Dragana Ahel

Michael L Nielsen

Rebecca Smith

Ivan Ahel

Affiliations

Soon will be listed here.

Abstract

PARP14 is a mono-ADP-ribosyl transferase involved in the control of immunity, transcription, and DNA replication stress management. However, little is known about the ADP-ribosylation activity of PARP14, including its substrate specificity or how PARP14-dependent ADP-ribosylation is reversed. We show that PARP14 is a dual-function enzyme with both ADP-ribosyl transferase and hydrolase activity acting on both protein and nucleic acid substrates. In particular, we show that the PARP14 macrodomain 1 is an active ADP-ribosyl hydrolase. We also demonstrate hydrolytic activity for the first macrodomain of PARP9. We reveal that expression of a PARP14 mutant with the inactivated macrodomain 1 results in a marked increase in mono(ADP-ribosyl)ation of proteins in human cells, including PARP14 itself and antiviral PARP13, and displays specific cellular phenotypes. Moreover, we demonstrate that the closely related hydrolytically active macrodomain of SARS2 Nsp3, Mac1, efficiently reverses PARP14 ADP-ribosylation in vitro and in cells, supporting the evolution of viral macrodomains to counteract PARP14-mediated antiviral response.

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