Hibernating ribosomes exhibit chaperoning activity but can resist unfolded protein‐mediated subunit dissociation

Ribosome hibernation is a prominent cellular strategy to modulate protein synthesis during starvation and the stationary phase of bacterial cell growth. Translational suppression involves the formation of either factor‐bound inactive 70S monomers or dimeric 100S hibernating ribosomal complexes, the biological significance of which is poorly understood. Here, we demonstrate that the Escherichia coli 70S ribosome associated with stationary phase factors hibernation promoting factor or protein Y or ribosome‐associated inhibitor A and the 100S ribosome isolated from both Gram‐negative and Gram‐positive bacteria are resistant to unfolded protein‐mediated subunit dissociation and subsequent degradation by cellular ribonucleases. Considering that the increase in cellular stress is accompanied by accumulation of unfolded proteins, such resistance of hibernating ribosomes towards dissociation might contribute to their maintenance during the stationary phase. Analysis of existing structures provided clues on the mechanism of inhibition of the unfolded protein‐mediated disassembly in case of hibernating factor‐bound ribosome. Further, the factor‐bound 70S and 100S ribosomes can suppress protein aggregation and assist in protein folding. The chaperoning activity of these ribosomes is the first evidence of a potential biological activity of the hibernating ribosome that might be crucial for cell survival under stress conditions. The hibernating HPF or YfiA bound monomeric 70S ribosome and the 100S dimeric Ribosome in the presence of equimolar concentrations of the unfolded protein displays chaperoning activity and yields the folded protein. The hibernating ribosomes also do not undergo ribosome subunit dissociation in the presence of 5‐fold excess concentration of unfolded protein and are hence resistant to subsequent degradation by cellular nucleases.