A Pathway for the Transmission of Allosteric Signals in the Ribosome through a Network of RNA Tertiary Interactions

There are a large number of tertiary contacts between nucleotides in 23 S rRNA, but which are of functional importance is not known. Disruption of one between A2662 in the sarcin/ricin loop (SRL) and A2531 in the peptidyl-transferase center (PTC) has adverse effects on cell growth and on the ability of ribosomes to catalyze some but not other partial reactions of elongation. A lethal A2662C mutation is suppressed by a concomitant lethal A2531 mutation. Ribosomes with non-lethal A2531 mutations, treated with base-specific reagents, have alterations of nucleotides in the PTC (home of A2531) and, more significantly, in nucleotides in the SRL and in the GTPase center. The results suggest that the function of ribosomal centers is coordinated by a set of sequential conformational changes in rRNA that are a response to signals transmitted through a network of tertiary interactions.