title: Poly(ADP-Ribose) polymerase 1 (PARP-1) regulates ribosomal biogenesis in Drosophila nucleoli.
abstract: Poly(ADP-ribose) polymerase 1 (PARP1), a nuclear protein, utilizes NAD to synthesize poly(AD-Pribose) (pADPr), resulting in both automodification and the modification of acceptor proteins. Substantial amounts of PARP1 and pADPr (up to 50%) are localized to the nucleolus, a subnuclear organelle known as a region for ribosome biogenesis and maturation. At present, the functional significance of PARP1 protein inside the nucleolus remains unclear. Using PARP1 mutants, we investigated the function of PARP1, pADPr, and PARP1-interacting proteins in the maintenance of nucleolus structure and functions. Our analysis shows that disruption of PARP1 enzymatic activity caused nucleolar disintegration and aberrant localization of nucleolar-specific proteins. Additionally, PARP1 mutants have increased accumulation of rRNA intermediates and a decrease in ribosome levels. Together, our data suggests that PARP1 enzymatic activity is required for targeting nucleolar proteins to the proximity of precursor rRNA; hence, PARP1 controls precursor rRNA processing, post-transcriptional modification, and pre-ribosome assembly. Based on these findings, we propose a model that explains how PARP1 activity impacts nucleolar functions and, consequently, ribosomal biogenesis.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Ernest K
authors.initials: EK
authors.lastname: Boamah
authors.forename: Elena
authors.initials: E
authors.lastname: Kotova
authors.forename: Mikael
authors.initials: M
authors.lastname: Garabedian
authors.forename: Michael
authors.initials: M
authors.lastname: Jarnik
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Tulin
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002466:Cell Nucleolus / Q000201:enzymology / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism*; D005786:Gene Expression Regulation; D017404:In Situ Hybridization, Fluorescence; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics* / Q000378:metabolism*; D034622:RNA Interference; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012335:RNA, Ribosomal / Q000235:genetics* / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; D012322:RNA Precursors; D012335:RNA, Ribosomal; D011064:Poly Adenosine Diphosphate Ribose; C524850:Parp protein, Drosophila; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases