PARP15

PARP15 (also known as ARTD7) is a member of the macrodomain-containing PARP family and functions as a mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of proteins and RNA, thereby regulating transcriptional and post-transcriptional cellular processes^[1][2][3]. Mechanistically, PARP15 contains macrodomains and a catalytic ADP-ribosyltransferase domain, linking ADP-ribosylation signaling to transcriptional regulation and RNA-associated functions^[2][4]. Recent structural and biochemical studies demonstrated that PARP15 localizes to stress granules, modifies RNA, and requires catalytic-domain dimerization for enzymatic activity, supporting a role in translational control and cellular stress responses^[2]. In disease-relevant contexts, evolutionary analyses have associated PARP15 with antiviral defense mechanisms, whereas human genetic studies identified PARP15 as a susceptibility locus in systemic capillary leak syndrome, implicating PARP15-mediated ADP-ribosylation in vascular inflammatory responses^[2][5]. Compared with its closely related paralog PARP14, PARP15 originated through partial gene duplication, possesses a simpler domain architecture, exhibits distinct NAD⁺-binding and automodification properties, and has evolved under lineage-specific selective pressures linked to host-virus interactions^[2]. For experimental applications, crystal structures of the PARP15 catalytic domain in complex with small-molecule inhibitors have provided a framework for the rational design of selective PARP-family inhibitors and for mechanistic studies of mono-ADP-ribosylation signaling^[6].