Macrodomain-containing proteins: regulating new intracellular functions of mono(ADP-ribosyl)ation

The function and regulation of poly(ADP-ribosyl)ation is partially understood. By contrast, little is known about intracellular mono(ADP-ribosyl)ation (MARylation) by ADP-ribosyl transferases. Recent findings indicate that MARylation regulates signalling and transcription by modifying key components in these processes, and that specific macrodomain-containing proteins 'read' and 'erase' this modification. Supplementary information The online version of this article (doi:10.1038/nrm3601) contains supplementary material, which is available to authorized users.
ADP-ribosylation of proteins was first described in the early 1960's, and today the function and regulation of poly(ADP-ribosyl)ation (PARylation) is partially understood. By contrast, little is known about intracellular mono(ADP-ribosyl)ation (MARylation) by ADP-ribosyl transferase (ART) enzymes, such as ARTD10. Recent findings indicate that MARylation regulates signalling and transcription by modifying key components in these processes. Emerging evidence also suggests that specific macrodomain-containing proteins, including ARTD8, macroD1, macroD2 and C6orf130, which are distinct from those affecting PARylation, interact with MARylation on target proteins to 'read' and 'erase' this modification. Thus, studying macrodomain-containing proteins is key to understanding the function and regulation of MARylation. Supplementary information The online version of this article (doi:10.1038/nrm3601) contains supplementary material, which is available to authorized users.