title: ARTD2 activity is stimulated by RNA.
abstract: ADP-ribosyltransferases (ARTs) are important enzymes that regulate the genotoxic stress response and the maintenance of genome integrity. ARTD1 (PARP1) and ARTD2 (PARP2) are homologous proteins that modify themselves and target proteins by the addition of mono- and poly-ADP-ribose (PAR) moieties. Both enzymes have been described to be involved in the genotoxic stress response. Here, we characterize cellular PAR formation on hydrogen peroxide (H2O2) or N-methyl-N'-methyl-nitro-N-nitrosoguanidine (MNNG) stress, in combination with application of the RNA polymerase I inhibitor Actinomycin D (ActD), known to cause accumulation of short RNA polymerase I-dependent rRNA transcripts. Intriguingly, co-treatment with ActD substantially increased H2O2- or MNNG-induced PAR formation. In cells, this enhancement was predominantly mediated by ARTD2 and not ARTD1. In vitro experiments confirmed that ARTD2 is strongly activated by RNA and that the N-terminal SAP domain is important for the binding to RNA. Thus, our findings identify a new activator of ARTD2-dependent ADP-ribosylation, which has important implications for the future analysis of the biological role of ARTD2 in the nucleus.
authors: Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland and Life Science Zurich Graduate School, University of Zurich, 8057 Zurich, Switzerland.
authors: Karolin
authors: K
authors: Léger
authors: Dominik
authors: D
authors: Bär
authors: Nataša
authors: N
authors: Savić
authors: Raffaella
authors: R
authors: Santoro
authors: Michael O
authors: MO
authors: Hottiger
mesh_terms: D000818:Animals; D002466:Cell Nucleolus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000378:metabolism
chemical_list: D012335:RNA, Ribosomal; D008769:Methylnitronitrosoguanidine; D003609:Dactinomycin; D011064:Poly Adenosine Diphosphate Ribose; D012313:RNA; D006861:Hydrogen Peroxide; C499320:PARP1 protein, human; C483041:PARP2 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases