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

Abstract

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.

Ribosomal dormancy at the nexus of ribosome homeostasis and protein synthesis

“…Interestingly, hibernating ribosomes in E. coli have been shown to assist in protein folding and in the suppression of protein aggregation. [ 76 ] Ribosomes also serve as crowding agents in the cytoplasm for modulating cellular diffusion and thus indirectly regulates many of the cellular processes. [ 77 ] Thus, possessing a sufficient number of ribosomes might be important for the survival of dormant cells.…”

Dietary L-arabinose-induced gut dysbiosis exacerbates bacterial infection

“…Y A promotes the formation of factor-bound inactive 70S ribosomes in stationary phase (43), and such factor-bound 70S ribosomes suppress protein aggregation (44). Next, a mutation in the potential binding sites of y A was performed to investigate the direct regulation of cAMP-CRP in vivo.…”

Ribosomal Hibernation-Associated Factors in Escherichia coli

“…Recently, some results concerning functions of these proteins and storage ribosomes have been reported in several bacterial species. The HPF-or RaiA-bound storage ribosomes of E. coli exhibit resistance to unfolded protein-mediated subunit dissociation and subsequent degradation by cellular ribonucleases, with the intrinsic chaperon activity retained to assist in protein folding [69]. The absence of HPF results in the loss of some proteins from the ribosome during incubation in the stationary phase [70,71]; furthermore, HPF protects ribosomes against degradation in the absence of mRNA by blocking the attack of ribonuclease [72][73][74].…”