Cleaves a beta-phosphate from the diphosphate groups in PP- InsP5 (diphosphoinositol pentakisphosphate) and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction (PubMed:10585413, PubMed:12370170, PubMed:9822604). InsP6 (inositol hexakisphosphate) is not a substrate (PubMed:9822604). Acts as a negative regulator of the ERK1/2 pathway (By similarity). Also able to catalyze the hydrolysis of dinucleoside oligophosphates, with diadenosine 5',5'''-P1,P6-hexaphosphate (Ap6A) and diadenosine 5',5'''- P1,P5-pentaphosphate (Ap5A) being the preferred substrates (PubMed:10419486, PubMed:12370170). The major reaction products are ADP and p4a from Ap6A and ADP and ATP from Ap5A (PubMed:12370170). Also able to hydrolyze 5-phosphoribose 1-diphosphate (PubMed:12370170). Acts as a decapping enzyme that modulates the stability of a subset of mRNAs implicated in cell motility (PubMed:26932476). Hydrolyzes monomethylated capped RNA after both the alpha- and beta-phosphates generating m7GMP + ppRNA and m7GDP + pRNA (PubMed:32727897). Can hydrolyze unmethylated capped RNAs (By similarity). Divalent cations zinc, magnesium and manganese determine its substrate specificity (PubMed:34788624). Exhibits diphosphoinositol polyphosphate phosphohydrolase in the presence of magnesium ions, diadenosine hexaphosphate hydrolase activity in the presence of manganese ions and endopolyphosphatase activity in the presence of zinc ions (PubMed:34788624). Plays an important role in limiting DNA damage and maintaining cell survival upon oxidative stress via its endopolyphosphatase activity (PubMed:34788624). {ECO:0000250|UniProtKB:Q9JI46, ECO:0000269|PubMed:10419486, ECO:0000269|PubMed:10585413, ECO:0000269|PubMed:12370170, ECO:0000269|PubMed:34788624, ECO:0000269|PubMed:9822604, ECO:0000305|PubMed:26932476}. This is the function of Ensembl gene identifier ENSG00000272325 (NUDT3, nudix hydrolase 3).