After the cap (GpppN) is set by the GTase, a first methylation occurs at N7 position of the guanine by a N7-MTase in the presence of methyl donor S-adenosyl methionine (SAM) yielding to a cap-0 (7mGpppN) followed by a further methylation that is achieved by a 2′-O-MTase at 2′- position of the ribose of the first transcribed nucleotide in RNA yielding cap-1 (7mGpppNm) (Scheme 1 ).