title: PARP12, an interferon-stimulated gene involved in the control of protein translation and inflammation.
abstract: 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.
authors.affiliation: Laboratoire d'Immunobiologie, Université Libre de Bruxelles, Gosselies, Belgium; Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Iain
authors.initials: I
authors.lastname: Welsby
authors.affiliation: Laboratoire d'Immunobiologie, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Hutin
authors.affiliation: Laboratoire de Biologie Moléculaire du Gène, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Cyril
authors.initials: C
authors.lastname: Gueydan
authors.affiliation: Laboratoire de Biologie Moléculaire du Gène, Université Libre de Bruxelles, Gosselies, Belgium; Center for Microscopy and Molecular Imaging (CMMI), Gosselies 6041, Belgium, and.
authors.forename: Veronique
authors.initials: V
authors.lastname: Kruys
authors.affiliation: Department of Immunobiology, Yale University, New Haven, Connecticut 06520.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rongvaux
authors.affiliation: Laboratoire d'Immunobiologie, Université Libre de Bruxelles, Gosselies, Belgium; Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium,. Electronic address: oleo@ulb.ac.be.
authors.forename: Oberdan
authors.initials: O
authors.lastname: Leo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003594:Cytoplasmic Granules / Q000378:metabolism; D004790:Enzyme Induction; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D016899:Interferon-beta / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D021381:Protein Transport; D015533:Transcriptional Activation; D025801:Ubiquitin / Q000378:metabolism; D016335:Zinc Fingers
chemical_list: D016328:NF-kappa B; D025801:Ubiquitin; D016899:Interferon-beta; C000594851:PARP12 protein, mouse; D011065:Poly(ADP-ribose) Polymerases
keywords: ADP-ribosylation; Interferon; Interferon-stimulated Gene (ISG); NF-κB (NF-κB); Poly(ADP-ribose) Polymerase (PARP); Stress Granule; Translation Regulation
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