Structural highlights
Function
NUD12_HUMAN Hydrolyzes NAD(P)H to NMNH and AMP (2',5'-ADP), and diadenosine diphosphate to AMP. Has also activity towards NAD(P)(+), ADP-ribose and diadenosine triphosphate. May act to regulate the concentration of peroxisomal nicotinamide nucleotide cofactors required for oxidative metabolism in this organelle.[1]
Publication Abstract from PubMed
RNA polymerase II transcripts receive a protective 5',5'-triphosphate-linked 7-methylguanosine (m(7)G) cap, and its removal by decapping enzymes like DCP2 is critical for initiation of RNA decay. Alternative RNA caps can be acquired when transcription initiation uses metabolites like nicotinamide adenine dinucleotide (NAD), generating NAD-RNAs. Here, we identify human NUDT12 as a cytosolic NAD-RNA decapping enzyme. NUDT12 is active only as homodimers, with each monomer contributing to creation of the two functional catalytic pockets. We identify an approximately 600-kDa dodecamer complex between bleomycin hydrolase (BLMH) and NUDT12, with BLMH being required for localization of NUDT12 to a few discrete cytoplasmic granules that are distinct from P-bodies. Both proteins downregulate gene expression when artificially tethered to a reporter RNA in vivo. Furthermore, loss of Nudt12 results in a significant upregulation of circadian clock transcripts in mouse liver. Overall, our study points to a physiological role for NUDT12 in the cytosolic surveillance of NAD-RNAs.
Decapping Enzyme NUDT12 Partners with BLMH for Cytoplasmic Surveillance of NAD-Capped RNAs.,Wu H, Li L, Chen KM, Homolka D, Gos P, Fleury-Olela F, McCarthy AA, Pillai RS Cell Rep. 2019 Dec 24;29(13):4422-4434.e13. doi: 10.1016/j.celrep.2019.11.108. PMID:31875550[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Abdelraheim SR, Spiller DG, McLennan AG. Mammalian NADH diphosphatases of the Nudix family: cloning and characterization of the human peroxisomal NUDT12 protein. Biochem J. 2003 Sep 1;374(Pt 2):329-35. doi: 10.1042/BJ20030441. PMID:12790796 doi:http://dx.doi.org/10.1042/BJ20030441
- ↑ Wu H, Li L, Chen KM, Homolka D, Gos P, Fleury-Olela F, McCarthy AA, Pillai RS. Decapping Enzyme NUDT12 Partners with BLMH for Cytoplasmic Surveillance of NAD-Capped RNAs. Cell Rep. 2019 Dec 24;29(13):4422-4434.e13. doi: 10.1016/j.celrep.2019.11.108. PMID:31875550 doi:http://dx.doi.org/10.1016/j.celrep.2019.11.108
