Figure 6.

Decapping of NAD-RNAs by different mechanisms. Mechanism I: Hydrolysis of the pyrophosphate bond of NAD by Nudix hydrolases such as NudC or BsRppH. NAD-RNA is processed to 5’-monophosphorylated RNA, which contains the adenosine of NAD as the first nucleotide (5’-P-A-RNA) and NMN. Mechanism II: “DeNADding”—Removal of the NAD-cap by DXO1. The phosphodiester bond between NAD and the second nucleotide is hydrolysed, which releases NAD and shortened 5’-monophosporylated RNA. Mechanism III: Removal of nicotinamide by hydrolysis of the N-glyosidic bond: CD38 catalyses the removal of nicotinamide (NAM), thereby converting NAD-RNA into ADPR-RNA.