ADP-ribosylation of RNA in mammalian cells is mediated by TRPT1 and multiple PARPs.

RNA function relies heavily on posttranscriptional modifications. Recently, it was shown that certain PARPs and TRPT1 can ADP-ribosylate RNA in vitro. Traditionally, intracellular ADP-ribosylation has been considered mainly as a protein posttranslational modification.

Are PARPs promiscuous?

Post-translational modifications exist in different varieties to regulate diverse characteristics of their substrates, ultimately leading to maintenance of cell health. The enzymes of the intracellular poly(ADP-ribose) polymerase (PARP) family can transfer either a single ADP-ribose to targets, in a reaction called mono(ADP-ribosyl)ation or MARylation, or multiple to form chains of poly(ADP-ribose) or PAR. Traditionally thought to be attached to arginine or glutamate, recent data have added serine, tyrosine, histidine and others to the list of potential ADP-ribose acceptor amino acids.

ADP-ribosyltransferases, an update on function and nomenclature.

ADP-ribosylation, a modification of proteins, nucleic acids, and metabolites, confers broad functions, including roles in stress responses elicited, for example, by DNA damage and viral infection and is involved in intra- and extracellular signaling, chromatin and transcriptional regulation, protein biosynthesis, and cell death. ADP-ribosylation is catalyzed by ADP-ribosyltransferases (ARTs), which transfer ADP-ribose from NAD onto substrates. The modification, which occurs as mono- or poly-ADP-ribosylation, is reversible due to the action of different ADP-ribosylhydrolases.

ADP-ribosylation of RNA and DNA: from in vitro characterization to in vivo function.

The functionality of DNA, RNA and proteins is altered dynamically in response to physiological and pathological cues, partly achieved by their modification. While the modification of proteins with ADP-ribose has been well studied, nucleic acids were only recently identified as substrates for ADP-ribosylation by mammalian enzymes. RNA and DNA can be ADP-ribosylated by specific ADP-ribosyltransferases such as PARP1-3, PARP10 and tRNA 2'-phosphotransferase (TRPT1).

The Controversial Roles of ADP-Ribosyl Hydrolases MACROD1, MACROD2 and TARG1 in Carcinogenesis.

Post-translational modifications (PTM) of proteins are crucial for fine-tuning a cell's response to both intracellular and extracellular cues. ADP-ribosylation is a PTM, which occurs in two flavours: modification of a target with multiple ADP-ribose moieties (poly(ADP-ribosyl)ation or PARylation) or with only one unit (MARylation), which are added by the different enzymes of the PARP family (also known as the ARTD family). PARylation has been relatively well-studied, particularly in the DNA damage response.

Nucleolar-nucleoplasmic shuttling of TARG1 and its control by DNA damage-induced poly-ADP-ribosylation and by nucleolar transcription.

Macrodomains are conserved protein folds associated with ADP-ribose binding and turnover. ADP-ribosylation is a posttranslational modification catalyzed primarily by ARTD (aka PARP) enzymes in cells. ARTDs transfer either single or multiple ADP-ribose units to substrates, resulting in mono- or poly-ADP-ribosylation.

Processing of protein ADP-ribosylation by Nudix hydrolases.

ADP-ribosylation is a post-translational modification (PTM) of proteins found in organisms from all kingdoms of life which regulates many important biological functions including DNA repair, chromatin structure, unfolded protein response and apoptosis. Several cellular enzymes, such as macrodomain containing proteins PARG [poly(ADP-ribose) glycohydrolase] and TARG1 [terminal ADP-ribose (ADPr) protein glycohydrolase], reverse protein ADP-ribosylation. In the present study, we show that human Nudix (nucleoside diphosphate-linked moiety X)-type motif 16 (hNUDT16) represents a new enzyme class that can process protein ADP-ribosylation in vitro, converting it into ribose-5'-phosphate (R5P) tags covalently attached to the modified proteins.

Function and regulation of the mono-ADP-ribosyltransferase ARTD10.

The transfer of ADP-ribose from NAD(+) to a substrate by ADP-ribosyltransferases, ADP-ribosylation, is a multifunctional posttranslational modification. While many studies have addressed the function of poly-ADP-ribosylation, for example, in DNA repair, signaling, and gene transcription, little is known about the role of mono-ADP-ribosylation. Recent work describing the mono-ADP-ribosyltransferase ARTD10/PARP10 suggests that this enzyme affects apoptosis, NF-κB signaling, and DNA damage repair, at least in part dependent on its activity as mono-ADP-ribosyltransferase.

Macrodomain-containing proteins: regulating new intracellular functions of mono(ADP-ribosyl)ation.

ADP-ribosylation of proteins was first described in the early 1960's, and today the function and regulation of poly(ADP-ribosyl)ation (PARylation) is partially understood. By contrast, little is known about intracellular mono(ADP-ribosyl)ation (MARylation) by ADP-ribosyl transferase (ART) enzymes, such as ARTD10. Recent findings indicate that MARylation regulates signalling and transcription by modifying key components in these processes.

Expanding functions of intracellular resident mono-ADP-ribosylation in cell physiology.

Poly-ADP-ribosylation functions in diverse signaling pathways, such as Wnt signaling and DNA damage repair, where its role is relatively well characterized. Contrarily, mono-ADP-ribosylation by for example ARTD10/PARP10 is much less understood. Recent developments hint at the involvement of mono-ADP-ribosylation in transcriptional regulation, the unfolded protein response, DNA repair, insulin secretion and immunity.

Regulation of NF-κB signalling by the mono-ADP-ribosyltransferase ARTD10.

Adenosine diphosphate-ribosylation is a post-translational modification mediated by intracellular and membrane-associated extracellular enzymes and many bacterial toxins. The intracellular enzymes modify their substrates either by poly-ADP-ribosylation, exemplified by ARTD1/PARP1, or by mono-ADP-ribosylation. The latter has been discovered only recently, and little is known about its physiological relevance.

Activity-based assay for human mono-ADP-ribosyltransferases ARTD7/PARP15 and ARTD10/PARP10 aimed at screening and profiling inhibitors.

Poly(ADP-ribose) polymerases (PARPs) or diphtheria toxin like ADP-ribosyl transferases (ARTDs) are enzymes that catalyze the covalent modification of proteins by attachment of ADP-ribose units to the target amino acid residues or to the growing chain of ADP-ribose. A subclass of the ARTD superfamily consists of mono-ADP-ribosyl transferases that are thought to modify themselves and other substrate proteins by covalently adding only a single ADP-ribose moiety to the target. Many of the ARTD enzymes are either established or potential drug targets and a functional activity assay for them will be a valuable tool to identify selective inhibitors for each enzyme.

Macrodomain-containing proteins are new mono-ADP-ribosylhydrolases.

ADP-ribosylation is an important post-translational protein modification (PTM) that regulates diverse biological processes. ADP-ribosyltransferase diphtheria toxin-like 10 (ARTD10, also known as PARP10) mono-ADP-ribosylates acidic side chains and is one of eighteen ADP-ribosyltransferases that catalyze mono- or poly-ADP-ribosylation of target proteins. Currently, no enzyme is known that reverses ARTD10-catalyzed mono-ADP-ribosylation.

Recognition of mono-ADP-ribosylated ARTD10 substrates by ARTD8 macrodomains.

ADP-ribosyltransferases (ARTs) catalyze the transfer of ADP-ribose from NAD(+) onto substrates. Some ARTs generate in an iterative process ADP-ribose polymers that serve as adaptors for distinct protein domains. Other ARTs, exemplified by ARTD10, function as mono-ADP-ribosyltransferases, but it has been unclear whether this modification occurs in cells and how it is read.

Caspase-dependent cleavage of the mono-ADP-ribosyltransferase ARTD10 interferes with its pro-apoptotic function.

ADP-ribosylation is a post-translational modification that regulates various physiological processes, including DNA damage repair, gene transcription and signal transduction. Intracellular ADP-ribosyltransferases (ARTDs or PARPs) modify their substrates either by poly- or mono-ADP-ribosylation. Previously we identified ARTD10 (formerly PARP10) as a mono-ADP-ribosyltransferase, and observed that exogenous ARTD10 but not ARTD10-G888W, a catalytically inactive mutant, interferes with cell proliferation.