Beyond protein modification: the rise of non-canonical ADP-ribosylation

ADP-ribosylation has primarily been known as post-translational modification of proteins. As signalling strategy conserved in all domains of life, it modulates substrate activity, localisation, stability or interactions, thereby regulating a variety of cellular processes and microbial pathogenicity. Yet over the last years, there is increasing evidence of non canonical forms of ADP-ribosylation that are catalysed by certain members of the ADPribosyltransferase family and go beyond traditional protein ADP-ribosylation signalling. New macromolecular targets such as nucleic acids and new ADP-ribose derivatives have been established, notably extending the repertoire of ADP-ribosylation signalling. Based on the physiological relevance known so far, non-canonical ADP-ribosylation deserves its recognition next to the traditional protein ADP-ribosylation modification and which we therefore review in the following.

Automated summary

ADP-ribosylation is a post-translational modification of proteins that plays a crucial role in cellular processes and microbial pathogenicity. Recent studies have revealed non-canonical forms of ADP-ribosylation, including modifications of nucleic acids and the discovery of new ADP-ribose derivatives. The physiological relevance of non-canonical ADP-ribosylation deserves recognition alongside traditional protein ADP-ribosylation modification.