PARP12, an interferon-stimulated gene involved in the control of protein translation and inflammation

J Biol Chem. 2014 Sep 19;289(38):26642-26657. doi: 10.1074/jbc.M114.589515. Epub 2014 Aug 1.


Transcriptome analyses have recently identified PARP12, a member of a large family of ADP-ribosyl transferases, as an interferon-induced gene (ISG), whose function remains incompletely characterized. We demonstrate herein that PARP12 is a genuine ISG, whose expressed protein displays at least two distinct subcellular locations and related functions. Upon ectopic expression or exposure to oxidative stress, PARP12 is recruited to stress-granules (SGs), known sites of mRNA translational arrest. Accordingly, PARP12 was found to block mRNA translation, possibly upon association to the translational machinery. Both the N-terminal domain (containing an RNA-binding domain characterized by the presence of five CCCH-type Zn-fingers) and integrity of the catalytic domain are required for this suppressive function. In contrast, stimulation with LPS leads to the localization of PARP12 to p62/SQSTM1 (an adaptor protein involved in innate signaling and autophagy) containing structures, unrelated to SGs. Deletion of the N-terminal domain promotes the association of the protein to p62/SQSTM1, suggesting that the RNA-binding domain is responsible for the subcellular localization of PARP12. Association to p62/SQSTM1 was found to correlate with increased NF-κB signaling, suggesting a role for PARP12 in inflammation. Collectively, these observations suggest that PARP12 can alternate between two distinct subcellular compartments associated to two distinct cellular functions. The present work therefore identifies PARP12 as an ISG with a potential role in cellular defenses against viral infections.

Keywords: ADP-ribosylation; Interferon; Interferon-stimulated Gene (ISG); NF-κB (NF-κB); Poly(ADP-ribose) Polymerase (PARP); Stress Granule; Translation Regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cytoplasmic Granules / metabolism
  • Enzyme Induction
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Inflammation / enzymology
  • Interferon-beta / physiology
  • Mice
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Poly(ADP-ribose) Polymerases / genetics*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Protein Biosynthesis*
  • Protein Transport
  • Transcriptional Activation
  • Ubiquitin / metabolism
  • Zinc Fingers


  • NF-kappa B
  • Ubiquitin
  • Interferon-beta
  • PARP12 protein, mouse
  • Poly(ADP-ribose) Polymerases