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Updated: Jan 24, 2026

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
Published on: March 5, 2019
Structural and mechanistic basis of mammalian Nudt12 RNA deNADding
Ewa Grudzien-Nogalska1, Yixuan Wu2, Xinfu Jiao1
1Department Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, USA.
Abstract:
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 Mg2+ ions at 1.6 Å 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.
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