Inhibition of initiation of protein synthesis by 7-methylguanosine-5'-monophosphate.

Translation of rabbit globin mRNA in a wheat germ protein-synthesizing system is inhibited by the nucleotide 7-methylguanosine-5'-monophosphate (m7G5'p) but not by other guanosine nucleotides without the 7-methyl group or with the phosphate in a different position. Translation of RNA of tobacco mosaic virus and poly(A) + HeLa RNA is also inhibited by m7G5'p. We show that m7G5'p prevents the association of mRNA with ribosomal subunits to form an initiation complex. We propose that m7G5'p interacts with a site on initiation factor(s) or ribosomes which is involved in mRNA recognition, presumably by binding to the 5'-terminal sequence m7G5'ppp. m7G5'p does not inhibit translation of poly(U) and RNA of satellite tobacco necrosis virus, which do not have the 5'-terminal sequence m7G5'ppp. In the case of RNA of satellite tobacco necrosis virus, some stimulation of its translation is consistently observed in the presence of m7G5'p; possible interpretations of this finding are discussed.