ADP-Ribosylation of Cytidine: A Novel Nucleic Acid Modification Reversed by NADAR Hydrolases

Journal article

ADP-ribosylation of nucleic acids is a modification found in both eukaryotes and bacteria, where it contributes to genome maintenance but can also serve as a toxic mechanism used by bacterial toxins to disrupt essential cellular processes. This modification is catalysed by ADP-ribosyltransferases and can be reversed by antagonistic ADP-ribosylgylcohydrolase enzymes. To date, ADP-ribosylation of nucleic acid bases has been described only for adenosine, guanosine, and thymidine. Here we report the ADP-ribosylation of cytidine, catalysed by members of the pierisin family of bacterial toxins-ScARP (SCO5461) and Scabin. We also show that ADP-ribosylation of cytidine is reversible through removal by certain NADAR family proteins, including NADAR proteins from the bacterium Streptomyces coelicolor (SCO5665) and the sponge Amphimedon queenslandica, as well as YbiA-type NADAR proteins. The conservation of cytidine de-ADP-ribosylating activity of NADAR proteins across phylogenetically distant species suggests that this modification may have important physiological significance.

Authors: Mikolčević, P; Hloušek-Kasun, A; Schuller, M; Lu, Y; Pirović, E

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: MDPI
• Journal: Toxins
• Volume: 18
• Issue: 2
• Pages: 82
• Publication date: 2026-02-06
• Acceptance date: 2026-02-03
• DOI: 10.3390/toxins18020082
• EISSN: 2072-6651
• ISSN: 2072-6651
• Pmid: 41745748
• Language: English
• Keywords: Streptomyces; Nadar; Scarp/sco5461; Sco5665; Adp-ribosylation; Cytidine