| First Author | Grudzien-Nogalska E | Year | 2019 |
| Journal | Nat Chem Biol | Volume | 15 |
| Issue | 6 | Pages | 575-582 |
| PubMed ID | 31101919 | Mgi Jnum | J:280091 |
| Mgi Id | MGI:6368680 | Doi | 10.1038/s41589-019-0293-7 |
| Citation | Grudzien-Nogalska E, et al. (2019) Structural and mechanistic basis of mammalian Nudt12 RNA deNADding. Nat Chem Biol 15(6):575-582 |
| abstractText | We recently demonstrated that mammalian cells harbor nicotinamide adenine dinucleotide (NAD)-capped messenger RNAs that are hydrolyzed by the DXO deNADding enzyme. Here, we report that the Nudix protein Nudt12 is a second mammalian deNADding enzyme structurally and mechanistically distinct from DXO and targeting different RNAs. The crystal structure of mouse Nudt12 in complex with the deNADding product AMP and three Mg(2+) ions at 1.6 A resolution provides insights into the molecular basis of the deNADding activity in the NAD pyrophosphate. Disruption of the Nudt12 gene stabilizes transfected NAD-capped RNA in cells, and its endogenous NAD-capped mRNA targets are enriched in those encoding proteins involved in cellular energetics. Furthermore, exposure of cells to nutrient or environmental stress manifests changes in NAD-capped RNA levels that are selectively responsive to Nudt12 or DXO, respectively, indicating an association of deNADding to cellular metabolism. |
