RIBOSOMAL-RNA COMPLEMENTARITY WITHIN MESSENGER-RNAS - A POSSIBLE BASIS FOR MESSENGER-RNA-RIBOSOME INTERACTIONS AND TRANSLATIONAL CONTROL

Our recent demonstration that many eukaryotic mRNAs contain sequences complementary to rRNA led to the hypothesis that these sequences might mediate specific interactions between mRNAs and ribosomes and thereby affect translation. In the present experiments, the ability of comple mentary sequences to bind to rRNA was investigated by using photochemi cal cross-linking. RNA probes with perfect complementarity to 18S or 2 8S rRNA were shown to cross-link specifically to the corresponding rRN A within intact ribosomal subunits. Similar results were obtained by u sing probes based on natural mRNA sequences with varying degrees of co mplementarity to the 18S rRNA. RNase Il cleavage localized four such p robes to complementary regions of the 18S rRNA. The effects of complem entarity on translation were assessed by using the mRNA encoding ribos omal protein S15. This mRNA contains a sequence within its coding regi on that is complementary to the 18S rRNA at 20 of 22 nucleotides. RNA from an S15-luciferase fusion construct was translated in a cell-free lysate and compared with the translation of four related constructs th at were mutated to decrease complementarity to the 18S rRNA. These mut ations did not alter the amino acid sequence or the codon bias. A corr elation between complementarity and translation was observed; construc ts with less complementarity increased the amount of translation up to 54%. These findings raised the possibility that direct base-pairing o f particular mRNAs to rRNAs within ribosomes may function as a mechani sm of translational control.