Influence of 5'-terminal m7G and 2'--O-methylated residues on messenger ribonucleic acid binding to ribosomes.

Removal of 80% of the 5'-terminal 7-methyl-guanosine (m7G) from methylated reovirus mRNA by beta elimination results in a concomitant loss of the ability to bind to wheat germ ribosomes. The mRNA molecules that retain the m7G account for most of the residual binding. Removal of the m7G from all molecules in preparations of methylated reovirus and vesicular stomatitis virus mRNA reduces the extent of binding to wheat germ ribosomes from 80% to 5-7%. In the reticulocyte lysate, however, significant binding (17-34%) of the beta-eliminated viral RNAs occurs. This m7G-independent binding appears to be due to recognition by ribosomes of other structural features of the 5'-proximal sequences. Initiation complexes involving beta-eliminated animal virus mRNAs and rabbit reticulocyte ribosomes appear to be more stable than the more heterologous combination of the same viral mRNAs and wheat germ ribosomes. In addition, evidence is presented to show that the 2'-O-methylated nucleoside of the 5'-terminal cap has a positive influence on the ribosome binding of viral mRNA and of capped synthetic ribopolymers. A model involving recognition of multiple structural features of the 5'-terminal region of mRNA by ribosomes during initiation of protein synthesis is presented.