RNA triphosphatase is an essential mRNA processing enzyme that catalyzes the first step in mRNA cap formation. The RNA triphosphatases are not conserved among eukarya and fall into at least 2 mechanistically and structurally distinct families: 1) the divalent cation-dependent RNA triphosphatases of DNA viruses and fungi, and 2) the divalent cation-independent RNA triphosphatases of nematodes, mammals, and other metazoa.