PARP14 is a PARP with both ADP-ribosyl transferase and hydrolase activities

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  • Nina Đukić
  • Øyvind Strømland
  • Deeksha Munnur
  • Kang Zhu
  • Marion Schuller
  • Chatrin Chatrin
  • Pulak Kar
  • Lena Duma
  • Osamu Suyari
  • Johannes Gregor Matthias Rack
  • Domagoj Baretić
  • Dorian Richard Kenneth Crudgington
  • Joséphine Groslambert
  • Gerissa Fowler
  • Sven Wijngaarden
  • Evgeniia Prokhorova
  • Jan Rehwinkel
  • Herwig Schüler
  • Dmitri V. Filippov
  • Sumana Sanyal
  • Dragana Ahel
  • Rebecca Smith
  • Ivan Ahel

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.

Original languageEnglish
Article numbereadi2687
JournalScience Advances
Issue number37
Number of pages19
Publication statusPublished - 2023

ID: 368253380