Polyinosinate [poly(1)] inhibited transfer RNA methylases prepared from the cell-soluble fraction and the nucleolar fraction of Novikoff rat hepatoma cells. Polyinosinate-cytidylate duplex, polyinosinate-cytidylate copolymer, and other homopolymers such as polycytidylate and polyadenylate showed very little effect. The mechanism of inhibition has been attributed to specific interactions between the single-stranded poly(I) and the methylating enzymes. Methylases of individual bases were differentially inhibited by poly(I), adenine methylase to the greatest extent and guanine methylases to the least.
The methylation of bases of endogenous ribosomal precursor RNA in isolated nucleoli was also inhibited by poly(I), resulting in preferential inhibition of the methylation of adenine.
The methylation of ribose moieties of ribosomal precursor RNA in isolated nucleoli has been detected in all 16 of the possible alkali-stable dinucleotide monophosphates by an improved method for resolution of these O2′-methyl dinucleoside monophosphate compounds. Poly(I) caused nonuniform inhibition of methylation of ribose moieties, although the pattern differed from the inhibition of base methylation.
A potentially pervasive effect of poly(I) on cell metabolism and a potential rationale for use in cancer chemotherapy are hereby demonstrated.
An abstract of this work has appeared (26). This work was supported by USPHS Grant CA-10244 and by American Cancer Society Grant E-609.