| Title: |
Reversible RNA ADP-ribosylation on uracil bases |
| Authors: |
Lu, Yang; Tang, Li; Strømland, Øyvind; Chatrin, Chatrin; Zhu, Kang; Munnur, Deeksha; Groslambert, Joséphine; Mikolčević, Petra; Schüler, Herwig; Timinszky, Gyula; Gabant, Guillaume; Suskiewicz, Marcin J; Mikoč, Andreja; Aucagne, Vincent; Ahel, Dragana; Liu, Qiang; Ahel, Ivan |
| Contributors: |
Biotechnology and Biological Sciences Research Council; Wellcome Trust; CRUK; Guy Newton Fund; National Research Development and Innovation Office; European Union’s NextGeneration EU program; Chinese Academy of Sciences; National Natural Science Foundation of China; Zhongshan Municipal Bure of Science and Technology; Institut National du Cancer, Projets libres de Recherche; Région Centre-Val de Loire; European FEDER Program |
| Source: |
Nucleic Acids Research ; volume 54, issue 6 ; ISSN 0305-1048 1362-4962 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2026 |
| Description: |
ADP-ribosylation is a conserved modification that uses NAD+ as a co-substrate to regulate essential cellular processes, such as genome stability and transcription, with Poly(ADP-ribose) Polymerases (PARPs) serving as the major catalyzing enzymes in humans. Historically defined as a protein post-translational modification, ADP-ribosylation on nucleic acids has been increasingly recognized in recent years, particularly in bacterial systems, but remains poorly understood in higher organisms. Here, we identify human PARP10 as a candidate enzyme that ADP-ribosylates nucleic acid bases, showing apparent activity on uracil bases in RNA, and a relatively weaker activity toward thymine bases in DNA. Furthermore, we show that human TARG1, a neurodegenerative disorder-linked protein previously reported to hydrolyse thymine base ADP-ribosylation, also efficiently reverses uracil base ADP-ribosylation (U-ADPr). To improve the efficient characterization of the enzymes for U-ADPr reversal, we developed chemical probes. Using these probes, we demonstrated that human TARG1 and TARG1-like macrodomain proteins are the efficient hydrolases for U-ADPr reversal in humans, Drosophila melanogaster, and bacterial homologues. The widespread distribution of U-ADPr hydrolases among different organisms suggests the potential evolutionary conservation of U-ADPr as a biological signal. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/nar/gkag289 |
| Availability: |
https://doi.org/10.1093/nar/gkag289; https://academic.oup.com/nar/article-pdf/54/6/gkag289/67688405/gkag289.pdf |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.784D7EED |
| Database: |
BASE |