Reversible ADP-ribosylation of RNA

Deeksha Munnur, Edward Bartlett, Petra Mikolčević, Ilsa T. Kirby, Johannes Gregor Matthias Rack, Andreja Mikoč, Michael Cohen, Ivan Ahel

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5658-5669
Number of pages12
JournalNucleic acids research
Volume47
Issue number11
DOIs
StatePublished - Jun 20 2019

Fingerprint

Adenosine Diphosphate
RNA
ADP-ribosylarginine hydrolase
NAD
ADP Ribose Transferases
SARS Virus
Adenosine Diphosphate Ribose
Biological Phenomena
Chromatin Assembly and Disassembly
Hydrolases
DNA Repair
Polymers
Proteins
Nucleotides
Viruses
Bacteria
DNA

ASJC Scopus subject areas

  • Genetics

Cite this

Munnur, D., Bartlett, E., Mikolčević, P., Kirby, I. T., Matthias Rack, J. G., Mikoč, A., ... Ahel, I. (2019). Reversible ADP-ribosylation of RNA. Nucleic acids research, 47(11), 5658-5669. https://doi.org/10.1093/nar/gkz305

Reversible ADP-ribosylation of RNA. / Munnur, Deeksha; Bartlett, Edward; Mikolčević, Petra; Kirby, Ilsa T.; Matthias Rack, Johannes Gregor; Mikoč, Andreja; Cohen, Michael; Ahel, Ivan.

In: Nucleic acids research, Vol. 47, No. 11, 20.06.2019, p. 5658-5669.

Research output: Contribution to journalArticle

Munnur, D, Bartlett, E, Mikolčević, P, Kirby, IT, Matthias Rack, JG, Mikoč, A, Cohen, M & Ahel, I 2019, 'Reversible ADP-ribosylation of RNA', Nucleic acids research, vol. 47, no. 11, pp. 5658-5669. https://doi.org/10.1093/nar/gkz305
Munnur D, Bartlett E, Mikolčević P, Kirby IT, Matthias Rack JG, Mikoč A et al. Reversible ADP-ribosylation of RNA. Nucleic acids research. 2019 Jun 20;47(11):5658-5669. https://doi.org/10.1093/nar/gkz305
Munnur, Deeksha ; Bartlett, Edward ; Mikolčević, Petra ; Kirby, Ilsa T. ; Matthias Rack, Johannes Gregor ; Mikoč, Andreja ; Cohen, Michael ; Ahel, Ivan. / Reversible ADP-ribosylation of RNA. In: Nucleic acids research. 2019 ; Vol. 47, No. 11. pp. 5658-5669.
@article{156e2b076def44cf8efa770f700ff29e,
title = "Reversible ADP-ribosylation of RNA",
abstract = "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.",
author = "Deeksha Munnur and Edward Bartlett and Petra Mikolčević and Kirby, {Ilsa T.} and {Matthias Rack}, {Johannes Gregor} and Andreja Mikoč and Michael Cohen and Ivan Ahel",
year = "2019",
month = "6",
day = "20",
doi = "10.1093/nar/gkz305",
language = "English (US)",
volume = "47",
pages = "5658--5669",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "11",

}

TY - JOUR

T1 - Reversible ADP-ribosylation of RNA

AU - Munnur, Deeksha

AU - Bartlett, Edward

AU - Mikolčević, Petra

AU - Kirby, Ilsa T.

AU - Matthias Rack, Johannes Gregor

AU - Mikoč, Andreja

AU - Cohen, Michael

AU - Ahel, Ivan

PY - 2019/6/20

Y1 - 2019/6/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85067243887&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067243887&partnerID=8YFLogxK

U2 - 10.1093/nar/gkz305

DO - 10.1093/nar/gkz305

M3 - Article

C2 - 31216043

AN - SCOPUS:85067243887

VL - 47

SP - 5658

EP - 5669

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 11

ER -