PARP12

PARP12 is a zinc-finger-containing mono-ADP-ribosyltransferase that functions as an interferon-stimulated antiviral effector and regulates protein mono-ADP-ribosylation in innate immune responses^[1][6]. Mechanistically, PARP12 localizes to cytoplasmic stress granules through its zinc-finger domains, where it contributes to antiviral defense by repressing translation, interacting with viral RNA, and promoting restriction of viral replication^[1][7]. PARP12 also directly modifies viral targets, including Zika virus non-structural proteins NS1 and NS3, leading to their ubiquitination-associated proteasomal degradation and suppression of viral propagation^[6][7]. In experimental infection models, PARP12 restricts replication of multiple RNA viruses, including alphaviruses, flaviviruses, coronaviruses, and encephalomyocarditis virus, supporting its central role in host antiviral immunity^[7][2][3]. Recent studies further demonstrated that PARP12 is required for efficient restriction of viral macrodomain mutants and participates in interferon-dependent antiviral pathways^[3][4]. Compared with the related zinc-finger PARP family member PARP13/ZAP, which lacks catalytic ADP-ribosyltransferase activity and primarily mediates RNA recognition and degradation, PARP12 possesses intrinsic mono-ADP-ribosyltransferase activity and directly modifies protein substrates^[7]. Beyond antiviral signaling, PARP12 has been implicated in intracellular trafficking through MARylation-dependent regulation of transport machinery, indicating broader cellular functions that may influence disease-relevant pathways^[5]. Therefore, PARP12 represents a valuable experimental target for investigating ADP-ribosylation-dependent antiviral mechanisms and innate immune regulation^[1][7].