PARP12 TRANSLOCATION FROM THE GOLGI COMPLEX IS PART OF THE STRESS RESPONSE AND REQUIRES POLY-ADP-RIBOSE

The cellular events regulated by mono-ADP-ribosyltransfeases (mARTs) include functions as diverse as immune response, transcriptional control, cell survival and stress responses. It is well accepted that certain stress conditions, such as heat shock or oxidative stress, prevent protein synthesis by sequestering mRNAs and stalling translation pre-initiation complexes in cytoplamic structures known as stress granules. Here, also poly-ADPribosyl polymerases (PARPs) and poly-ADP-ribosyl glycohydrolases (PARG) are recruited and contribute to both assembly of these structures through poly-ADP-ribose synthesis and regulation of mRNAs translation. Among the stress granule-PARPs, we investigated the role played by PARP12 in HeLa cells under oxidative stress. Our data show that PARP12, a Golgi-complex localised mART, under stress challenge translocates from the Golgi complex to stress granules. Importantly, we have identified the molecular determinants regulating this translocation that relies on the sensing of poly-ADP ribose (PAR) through PARP12 WWE domains. Of note, our data point at a regulatory pathway that depends on a nuclear stimulus - the PAR itself or PARylated proteins - able to signal to the Golgi apparatus and to modulate PARP12 translocation with concomitant alteration of the organelle morphology and functions. Hence we propose that this talling of Golgi complex functions is part of the cellular stress response, associated to a reversible translocation of PARP12.