MacroD1 Is a Promiscuous ADP-Ribosyl Hydrolase Localized to Mitochondria

Agnew, Thomas; Munnur, Deeksha; Crawford, Kerryanne; Palazzo, Luca; Mikoč, Andreja; Ahel, Ivan

doi:10.3389/fmicb.2018.00020

Cited by 44 publications

(57 citation statements)

References 65 publications

(122 reference statements)

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“…All above mentioned hydrolases, except for ARH1 and ARH2, were able to remove ADP-ribosylation from either 5 or 3 phosphates at the end of RNA substrates (Figure 2A and B). Importantly, catalytically inactive mutants of MACROD1 (G270E) and ARH3 (D77A) (27,30) did not remove ADPr from phosphorylated-ssRNA (Fig-ure 2C), demonstrating that the enzymatic activity of these ADP-ribosylhydrolases is required for efficient removal of ADP-ribose from RNA phosphorylated ends. Together, these results demonstrate that ADP-ribosylation of phosphorylated-RNA oligos catalysed by PARP10 is a reversible process.…”

Section: Adp-ribosylation Of Rna Ends By Parp10 Is a Reversible Processmentioning

confidence: 98%

“…Recombinant protein was purified using TALON affinity resin according to standard procedure. Streptomyces coelicolor MacroD homologue (SCO6450) was obtained as described earlier (30).…”

Section: Plasmid and Protein Purificationmentioning

confidence: 99%

“…Mycobacterium tuberculosis (Mtb) DarG-macro was cloned with 155 N-terminal amino acids as described earlier (25). Catalytic domains of PARP11 (128-338aa) (35), MACROD1 (30,36), MACROD2 (19), TARG1 (17), PARG (37), NUDT16 (21) and ARH 1-3 (15) were purified as described earlier. Viral macrodomain-containing hydrolases from VEEV (38) and SARS Coronavirus (39) were prepared as described earlier.…”

Section: Plasmid and Protein Purificationmentioning

confidence: 99%

“…Furthermore, it was shown that DNA repair PARPs (PARP1, PARP2 and PARP3) can modify DNA on phosphates at DNA breaks (26)(27)(28)(29). The ADPr groups on phosphates at DNA breaks are efficiently removed by several cellular hydrolases, most notably by PARG, MACROD1/2, TARG1 and ARH3 (26,27,30).…”

Section: Introductionmentioning

confidence: 99%

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Reversible ADP-ribosylation of RNA

Munnur

Bartlett

Mikolčević

et al. 2019

Nucleic Acids Research

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129

189

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ADP-ribosylation is a reversible chemical modification catalysed by ADP-ribosyltransferases such as PARPs that utilize nicotinamide adenine dinucleotide (NAD+) as a cofactor to transfer monomer or polymers of ADP-ribose nucleotide onto macromolecular targets such as proteins and DNA. ADP-ribosylation plays an important role in several biological processes such as DNA repair, transcription, chromatin remodelling, host-virus interactions, cellular stress response and many more. Using biochemical methods we identify RNA as a novel target of reversible mono-ADP-ribosylation. We demonstrate that the human PARPs - PARP10, PARP11 and PARP15 as well as a highly diverged PARP homologue TRPT1, ADP-ribosylate phosphorylated ends of RNA. We further reveal that ADP-ribosylation of RNA mediated by PARP10 and TRPT1 can be efficiently reversed by several cellular ADP-ribosylhydrolases (PARG, TARG1, MACROD1, MACROD2 and ARH3), as well as by MACROD-like hydrolases from VEEV and SARS viruses. Finally, we show that TRPT1 and MACROD homologues in bacteria possess activities equivalent to the human proteins. Our data suggest that RNA ADP-ribosylation may represent a widespread and physiologically relevant form of reversible ADP-ribosylation signalling.

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Section: Adp-ribosylation Of Rna Ends By Parp10 Is a Reversible Processmentioning

confidence: 98%

“…Recombinant protein was purified using TALON affinity resin according to standard procedure. Streptomyces coelicolor MacroD homologue (SCO6450) was obtained as described earlier (30).…”

Section: Plasmid and Protein Purificationmentioning

confidence: 99%

Section: Plasmid and Protein Purificationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Reversible ADP-ribosylation of RNA

Munnur

Bartlett

Mikolčević

et al. 2019

Nucleic Acids Research

Self Cite

129

189

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show abstract

“…TARG1 degrades MAR by a different mechanism than PARG, by breaking the ester linkage between PAR and glutamate, an action that cannot be accomplished by PARG (186). MacroD1 exists primarily in the mitochondria and has low specificity in its ADPR hydrolase activity, removing a broad spectrum of ADP-ribosyl moieties with ester linkages from proteins, DNA, and small molecules (528). MacroD2, in addition to its ADP-ribosylhydrolase function, acts mainly in the cytoplasm, where it selectively deacetylates O-acetyl-ADP-ribose (529).…”

Section: Marylation and Its Reversalmentioning

confidence: 99%

Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity

Brady

Goel

Johnson

2019

Microbiol Mol Biol Rev

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SUMMARYThe literature review presented here details recent research involving members of the poly(ADP-ribose) polymerase (PARP) family of proteins. Among the 17 recognized members of the family, the human enzyme PARP1 is the most extensively studied, resulting in a number of known biological and metabolic roles. This review is focused on the roles played by PARP enzymes in host-pathogen interactions and in diseases with an associated inflammatory response. In mammalian cells, several PARPs have specific roles in the antiviral response; this is perhaps best illustrated by PARP13, also termed the zinc finger antiviral protein (ZAP). Plant stress responses and immunity are also regulated by poly(ADP-ribosyl)ation. PARPs promote inflammatory responses by stimulating proinflammatory signal transduction pathways that lead to the expression of cytokines and cell adhesion molecules. Hence, PARP inhibitors show promise in the treatment of inflammatory disorders and conditions with an inflammatory component, such as diabetes, arthritis, and stroke. These functions are correlated with the biophysical characteristics of PARP family enzymes. This work is important in providing a comprehensive understanding of the molecular basis of pathogenesis and host responses, as well as in the identification of inhibitors. This is important because the identification of inhibitors has been shown to be effective in arresting the progression of disease.

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Mitochondria are devoid of poly(ADP‐ribose)polymerase‐1, but harbor its product oligo(ADP‐ribose)

Köritzer

Blenn

Bürkle

et al. 2021

J of Cellular Biochemistry

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There are conflicting data about localization of poly(ADP-ribose)polymerase-1 and its product poly(ADP-ribose) in mitochondria. To finally clarify the discussion, we investigated with biochemical and cell biological methods the potential presence of poly(ADP-ribose) polymerase-1 in these organelles. Our data show that endogenous and overexpressed poly(ADP-ribose)polymerase 1 is only localized to the nucleus with a clear exclusion of cytosolic compartments. In addition, highly purified mitochondria devoid of nuclear contaminations do not contain poly(ADP-ribose)polymerase-1. Although no poly (ADP-ribose)polymerase-1 enzyme is detectable in mitochondria, a shorter variant of its product poly(ADP-ribose) is present, associated specifically with a small subset of mitochondrial proteins as revealed by immunoprecipitation and protein fingerprint analysis. These proteins are located at key-points of the Krebs-cycle, are chaperones involved in mitochondrial functionality and quality-control, and are RNA-binding proteins important for transcript stability, respectively. Of note, despite the fact that especially poly(ADP-ribose) polymerase-1 is its own major target for modification, we could not detect this enzyme by mass spectrometry in these organelles. These data suggests a new way of targeted nuclear-mitochondrial signaling, mediated by nuclear poly (ADP-ribosyl)ation dependent on poly(ADP-ribose)polymerase-1.

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MacroD1 Is a Promiscuous ADP-Ribosyl Hydrolase Localized to Mitochondria

Cited by 44 publications

References 65 publications

Reversible ADP-ribosylation of RNA

Reversible ADP-ribosylation of RNA

Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity

Mitochondria are devoid of poly(ADP‐ribose)polymerase‐1, but harbor its product oligo(ADP‐ribose)

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