The adenosine analogs neplanocin A and deazaneplanocin A were observed to inhibit the in vivo guanine-7-methylation of mRNA cap structure using a new assay for hypomethylated RNA. Treatment of cultured mammalian cells with these adenosine analogs resulted in the same extent of hypomethylation of cap structure as did ethionine injection in mice. Neplanocin A and its non-metabolizable analog 3-deazaneplanocin A show the same maximal level of inhibition of methylation suggesting that these adenosine analogs exert their effects by elevating S-adenosylhomocysteine levels rather than by conversion to other inhibitory compounds.
