PARP12-dependent mono-ADP-ribosylation of Golgin-97 is involved in the control of intracellular membrane traffic

ADP-ribosylation is a widespread post-translational modification regulating a vast array of cellular processes, ranging from DNA-damage repair, transcription and cell-cycle progression, to viral infection and stress response. Many of these functions are mediated by enzymes of the poly-ADP-ribosyl polymerase (PARP) family; the mechanism of action and substrates of the different PARPs remain however to be fully elucidated. In order to identify the specific substrates of PARP activities, a fundamental step to elucidate their physiological function, we selected PARP12 that based on our initial investigation showed a robust catalytic activity. The main role reported so far for PARP12 refers to mRNA regulation during stress response. Here, we present a new function of PARP12 under non-stressing conditions, showing the pathways in which this enzyme is involved through the identification of its substrates. We show that PARP12 is able to interact and modify Golgin-97, a trans-Golgi-localised protein that is involved in the maintenance of the Golgi architecture and in the regulation of vesicular traffic. Further, we demonstrate that PARP12 specifically controls Golgin-97 mediated trafficking routes, pointing at a novel role of this post-translational modification in the regulation of intracellular membrane traffic. Bioinformatics and mutagenesis approaches have been undertaken to further dissect the molecular mechanism at the base of this pathway.