PARP1 activation regulates the PARP12 translocation from the Golgi complex to stress granules during oxidative stress

Stress granules are transient structures that are formed in the cytoplasm of cells following stress challenge. They contribute to the regulation of translation by clustering mRNAs as well as several signaling proteins to modulate cell metabolism and survival until the stress relief. Recently, poly-ADP-ribose (PAR), the reaction product of poly-ADP-ribosylpolymerases (PARPs), has been demonstrated to play a role in the assembly and maintenance of stress granules. In addition, specific PARPs (PARPs-5,-12,-13,-15) localise at these structures regulating mRNAs translation in response to stress. However the molecular mechanism underlying this event remains unclear. Among the stress-granule PARPs, we focused on the behavior of PARP12 in HeLa cells under oxidative stress. Here we show that PARP12 is a Golgi localised mono-ADP-ribosyltransferase that under the stress challenge translocates from the Golgi complex to stress granules in a reversible manner. Importantly, we show that PARP12 translocation occurs following the release of nuclear PAR (free PAR or poly-ADP ribosylated proteins) due to PARP1 activation and that PAR binding is mediated through the PARP12 WWE domain. PARP1 knocking down or selective inhibition of PARP1 catalytic activity impaired PARP12 recruitment to stress granules. Of note, we show that PARP12 translocation from the Golgi complex is linked to alteration of the organelle morphology and functions.