PARP14 controls the nuclear accumulation of a subset of type I Interferon-inducible proteins [RNA-seq1]

The enzymes of the poly-ADP-ribose polymerase (PARP) super-family control many relevant cellular processes, but a precise understanding of their activities in different physiological or disease contexts is largely incomplete. We found that transcription of several PARP genes was dynamically regulated upon macrophage activation by several inflammatory stimuli. Specifically, PARP14 was strongly induced by endotoxin stimulation and translocated to the nucleus in stimulated cells. Quantitative mass spectrometry analysis showed that PARP14 bound to a group of interferon-stimulated gene (ISG)-encoded proteins, most with an unknown function, and it was required for their nuclear accumulation. Moreover, PARP14 depletion attenuated transcription of primary antiviral response genes regulated by the transcription factor IRF3, including Ifnb1, thus reducing IFNß production and activation of ISGs involved in the secondary antiviral response. Overall, these data hint at a role of PARP14 in the control of antimicrobial responses and specifically in nuclear activities of a subgroup of ISG-encoded proteins. Overall design: mRNA sequencing of differentially expressed genes in PARP14 WT and KO RAW 264.7 cells, upon: no treatment, LPS, Jak inhibitor or LPS plus Jak inhibitor treatment.

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Caprara G, Prosperini E, Piccolo V, Sigismondo G, Melacarne A, Cuomo A, Boothby M, Rescigno M, Bonaldi T, Natoli G