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.
Highlights
Apoptosis plays a key role in maintaining homeostasis for the survival in multicellular organism, especially under pathophysiological stresses[1,2,3]
The SFB-tagged mutant tPARP1 (mtPARP1) was stably expressed in PARP1deficient 293T cells, and the soluble fraction was isolated followed by tandem affinity purifications
We found that POLR3A, POLR3B, and POLR3F, the three subunits of RNA polymerase III (Pol III) complex, were the common interacting proteins with both mtPARP1 and mTARG1 (Fig. 1d and Supplementary Tables S1 and S2)
Summary
Apoptosis plays a key role in maintaining homeostasis for the survival in multicellular organism, especially under pathophysiological stresses[1,2,3]. One prominent substrate of caspases is poly (ADP-ribose) polymerase 1 (PARP1)[10,11]. PARP1 is the founding member of PARP family and catalyzes poly(ADP-ribosyl)ation ( known as PARylation) on protein substrates[14,15,16,17]. It contains multiple domains, including the N-terminal zinc finger motifs, the BRCT domain, the WGR domain and the C-terminal
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