MonoADPribosyltransferases

Mono-ADP-ribosylation (MARylation) is a reversible post-translational modification in which a single ADP-ribose unit is transferred from nicotinamide adenine dinucleotide (NAD+) to target proteins or substrates. This modification is distinct from poly-ADP-ribosylation (PARylation), which forms long chains of ADP-ribose.

The enzymatic activity is carried out by mono-ADP-ribosyltransferases (mARTs). In eukaryotes, several PARP family members possess MARylation activity, contributing to the regulation of diverse cellular processes. In bacteria and some pathogens, toxin-encoded MARyltransferases modify host proteins to disrupt signaling and trafficking, aiding infection.

The ADP-ribose donor is NAD+, and the transfer typically attaches the ADP-ribose to specific amino acid residues such as arginine, serine, or others, depending on the enzyme and substrate. MARylation is reversible; cellular hydrolases, including members of the ARH and macro domain families, can remove the ADP-ribose, restoring the unmodified state of the substrate.

Biological roles for MARylation are diverse. It modulates signaling pathways, transcription, and DNA repair, and it participates in stress responses and innate immune signaling. The modification can affect protein activity, interactions, localization, and stability. Dysregulation of MARylation has been linked to diseases such as cancer and neurodegenerative disorders, highlighting its integration with cellular energy metabolism and NAD+-dependent signaling networks.

Detection and study of MARylation employ techniques such as ADP-ribose–specific antibodies, binding reagents, and mass spectrometry. Therapeutic interest exists in developing selective modulators of MARylation enzymes to influence disease-related pathways.