Arabidopsis DXO1 activates RNMT1 to methylate the mRNA guanosine cap

Arabidopsis DXO1 is a member of the eukaryotic DXO family of decapping enzymes for NAD-capped RNAs. Here the authors show that DXO1 is an essential component in canonical m(7)G capping of mRNA and activates RNMT1 which methylates the guanosine cap to form the m(7)G cap. Eukaryotic messenger RNA (mRNA) typically contains a methylated guanosine (m(7)G) cap, which mediates major steps of mRNA metabolism. Recently, some RNAs in both prokaryotic and eukaryotic organisms have been found to carry a non-canonical cap such as the NAD cap. Here we report that Arabidopsis DXO family protein AtDXO1, which was previously known to be a decapping enzyme for NAD-capped RNAs (NAD-RNA), is an essential component for m(7)G capping. AtDXO1 associates with and activates RNA guanosine-7 methyltransferase (AtRNMT1) to catalyze conversion of the guanosine cap to the m(7)G cap. AtRNMT1 is an essential gene. Partial loss-of-function mutations of AtRNMT1 and knockout mutation of AtDXO1 reduce m(7)G-capped mRNA but increase G-capped mRNAs, leading to similar pleiotropic phenotypes, whereas overexpression of AtRNMT1 partially restores the atdxo1 phenotypes. This work reveals an important mechanism in m(7)G capping in plants by which the NAD-RNA decapping enzyme AtDXO1 is required for efficient guanosine cap methylation.