Reversible RNA ADP-ribosylation on uracil bases - PubMed
6 hours ago
- #RNA modification
- #ADP-ribosylation
- #PARP10
- ADP-ribosylation is a conserved modification using NAD+ and primarily catalyzed by PARPs in humans, regulating cellular processes like genome stability and transcription.
- Human PARP10 is identified as an enzyme that ADP-ribosylates nucleic acid bases, showing strong activity on uracil in RNA and weaker activity on thymine in DNA.
- Human TARG1, linked to neurodegenerative disorders, efficiently reverses uracil base ADP-ribosylation (U-ADPr) and acts as a hydrolase for this modification.
- Chemical probes were developed to characterize U-ADPr reversal enzymes, revealing TARG1 and TARG1-like macrodomain proteins as efficient hydrolases across humans, Drosophila, and bacteria.
- The widespread presence of U-ADPr hydrolases across organisms suggests evolutionary conservation of U-ADPr as a biological signal.