Abstract
Caspase-mediated cleavage of PARP1 is a surrogate marker for apoptosis. However, the biological significance of PARP1 cleavage during apoptosis is still unclear. Here, using unbiased protein affinity purification, we show that truncated PARP1 (tPARP1) recognizes the RNA polymerase III (Pol III) complex in the cytosol. tPARP1 mono-ADP-ribosylates RNA Pol III in vitro and mediates ADP-ribosylation of RNA Pol III during poly(dA-dT)-stimulated apoptosis in cells. tPARP1-mediated activation of RNA Pol III facilitates IFN-β production and apoptosis. In contrast, suppression of PARP1 or expressing the non-cleavable form of PARP1 impairs these molecular events. Taken together, these studies reveal a novel biological role of tPARP1 during cytosolic DNA-induced apoptosis.