Nudix hydrolase 16 (NUDT16)

Nudix hydrolase 16 (NUDT16) is a member of the Nudix hydrolase superfamily, functioning as a dimeric metalloenzyme that catalyzes the hydrolysis of nucleoside diphosphate bonds in diverse substrates. It acts as a decapping enzyme for small nucleolar RNA (snoRNA), particularly U8 snoRNA, as well as capped mRNA, removing methylated guanosine caps in the presence of divalent cations such as Mg²⁺ or Mn²⁺[2][4][6]. Beyond its canonical RNA decapping activity, NUDT16 plays "housecleaning" roles: it eliminates hazardous (deoxy)inosine diphosphate and ADP-ribosylated nucleotide derivatives from the nuclear and cytoplasmic pools, thereby protecting genomic integrity and regulating cell proliferation[1][3][5]. Structurally, NUDT16 consists of a Nudix motif that coordinates substrate and metal ion binding and regulates substrate specificity[1][5]. Loss of NUDT16 function leads to DNA single-strand breaks, increased cell arrest, and impaired cell growth, highlighting its critical cellular role[1][3][5]. Its activity and specificity are tightly regulated by substrate and product binding, with IMP (inosine monophosphate) acting as a feedback inhibitor[3]. Currently, no drugs are clinically known to target NUDT16 directly.

Other names

U8 snoRNA-decapping enzymeIDPaseNudix motif 16FLJ31265IDP phosphataseInosine diphosphate phosphataseNucleoside diphosphate-linked moiety X motif 16U8 snoRNA-binding protein H29Km7GpppN-mRNA hydrolasetesticular tissue protein Li 129

Hydrolysis of nucleoside diphosphates (e.g., inosine diphosphate, ADP-ribose). Decapping of mRNA and snoRNA by removal of methylated guanosine cap structures[2][4][6]. Degradation of hazardous nucleotide analogs, prevention of accumulation in cells[2][3][5].