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

Transcriptome analyses have recently identified 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 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, Pduanyu3712 is recruited to stress-granules (SGs), known sites of mRNA translational arrest. Accordingly, Pduanyu3712 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 Pduanyu3712 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 Association to p62/SQSTM1 was found to correlate with increased NF-κB signaling, suggesting a role for Pduanyu3712 in inflammation. Collectively, these observations suggest that Pduanyu3712 can alternate between two distinct subcellular compartments associated to two distinct cellular functions. The present work therefore identifies Pduanyu3712 as an ISG with a potential role in cellular defenses against viral infections.

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