Inhibition of ribosomal subunit association and protein synthesis by oligonucleotides corresponding to defined regions of 18S rRNA and 5S rRNA.

Strong complementarity between a conserved sequence near the 3' end of 18S (16S) rRNA of the small ribosomal subunit and a conserved sequence in the 5S rRNA of the large ribosomal subunit supported the suggestion that base-paired interaction between the two RNA molecules could be responsible for the reversible association of ribosomal subunits during protein synthesis. If this were true then oligonucleotides corresponding to defined regions of the 18S and 5S rRNAs should have profound effects on the association of ribosomal subunits and protein synthesis. In this report we show that oligonucleotides, corresponding to a defined region of eukaryotic 18S rRNA, when bound to wheat embryo 60S ribosomal subunits, inhibited association with 40S ribosomal subunits and also inhibited in vitro protein synthesis. Similarly oligonucleotides corresponding to a defined region of 5S rRNA when bound to 40S ribosomal subunits also inhibited the formation of 80S ribosomes and in vitro protein synthesis. The minimum sequences responsible for the inhibition of ribosomal subunit association and in vitro protein synthesis corresponded to the 5' strand of the m2(6)A m2(6)A hairpin structure near the 3' end of 18S rRNA and nucleotides 91-100 of 5S rRNA which are complementary to each other. Sequences at identical positions of Escherichia coli 16S and 5S rRNAs are also complementary to each other.