Reversible ADP-ribosylation of RNA

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

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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

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ASJC Scopus subject areas

  • Genetics

Cite this

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