Biomaterial Database

Poly(ADP-ribosyl)ation of heterogeneous nuclear ribonucleoproteins modulates splicing. 2009

Yingbiao Ji, and Alexei V Tulin

Fox Chase Cancer Center, Philadelphia, PA 19111, USA.

The biological functions of poly(ADP-ribosyl)ation of heterogeneous nuclear ribonucleoproteins (hnRNPs) are not well understood. However, it is known that hnRNPs are involved in the regulation of alternative splicing for many genes, including the Ddc gene in Drosophila. Therefore, we first confirmed that poly(ADP-ribose) (pADPr) interacts with two Drosophila hnRNPs, Squid/hrp40 and Hrb98DE/hrp38, and that this function is regulated by Poly(ADP-ribose) Polymerase 1 (PARP1) and Poly(ADP-ribose) Glycohydrolase (PARG) in vivo. These findings then provided a basis for analyzing the role of pADPr binding to these two hnRNPs in terms of alternative splicing regulation. Our results showed that Parg null mutation does cause poly(ADP-ribosyl)ation of Squid and hrp38 protein, as well as their dissociation from active chromatin. Our data also indicated that pADPr binding to hnRNPs inhibits the RNA-binding ability of hnRNPs. Following that, we demonstrated that poly(ADP-ribosyl)ation of Squid and hrp38 proteins inhibits splicing of the intron in the Hsr omega-RC transcript, but enhances splicing of the intron in the Ddc pre-mRNA. Taken together, these findings suggest that poly(ADP-ribosyl)ation regulates the interaction between hnRNPs and RNA and thus modulates the splicing pathways.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011064	Poly Adenosine Diphosphate Ribose	A polynucleotide formed from the ADP-RIBOSE moiety of nicotinamide-adenine dinucleotide (NAD) by POLY(ADP-RIBOSE) POLYMERASES.	Poly ADP Ribose,Poly(ADP-Ribose),Poly-ADPR,Poly-Adenosine Diphosphate-Ribose,ADP Ribose, Poly,Diphosphate-Ribose, Poly-Adenosine,Poly ADPR,Ribose, Poly ADP
D011065	Poly(ADP-ribose) Polymerases	Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.	ADP-Ribosyltransferase (Polymerizing),Poly ADP Ribose Polymerase,Poly(ADP-Ribose) Synthase,Poly(ADP-ribose) Polymerase,PARP Polymerase,Poly ADP Ribose Transferase,Poly ADP-Ribose Synthase,Poly(ADP-Ribose) Transferase,Poly(ADPR) Polymerase,Poly(ADPribose) Polymerase,Poly ADP Ribose Synthase,Polymerase, PARP,Synthase, Poly ADP-Ribose
D002467	Cell Nucleus	Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)	Cell Nuclei,Nuclei, Cell,Nucleus, Cell
D002843	Chromatin	The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.	Chromatins
D004330	Drosophila	A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.	Fruit Fly, Drosophila,Drosophila Fruit Flies,Drosophila Fruit Fly,Drosophilas,Flies, Drosophila Fruit,Fly, Drosophila Fruit,Fruit Flies, Drosophila
D006026	Glycoside Hydrolases	Any member of the class of enzymes that catalyze the cleavage of the glycosidic linkage of glycosides and the addition of water to the resulting molecules.	Endoglycosidase,Exoglycosidase,Glycohydrolase,Glycosidase,Glycosidases,Glycoside Hydrolase,Endoglycosidases,Exoglycosidases,Glycohydrolases,Hydrolase, Glycoside,Hydrolases, Glycoside
D000071137	Poly (ADP-Ribose) Polymerase-1	A poly(ADP-ribose) polymerase that contains two ZINC FINGERS in its N-terminal DNA-binding region. It modifies NUCLEAR PROTEINS involved in chromatin architecture and BASE EXCISION REPAIR with POLY ADENOSINE DIPHOSPHATE RIBOSE.	NAD+ ADP-ribosyltransferase-1,PARP-1 Protein,PARP1 Protein,Poly (ADP-Ribose) Synthase-1,NAD+ ADP ribosyltransferase 1,PARP 1 Protein
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia