Falling asleep: the importance of ribosome hibernation in bacteria

SUMMARY The biogenesis of ribosomes and protein synthesis are among the most energy-consuming processes in living cells and therefore rate-limiting for growth, making them key targets for controlling the growth of competitors, predators, and pathogens. Cells also restrict their own protein synthesis under nutrient limitation or other stress conditions. A universally conserved strategy involves ribosome hibernation, in which specialized factors reversibly silence ribosomes. This protects ribosomes from being degraded by RNases and proteases, and at the same time allows for their fast reactivation when conditions improve. In bacteria, multiple hibernation factors act in parallel through distinct mechanisms. Well-characterized factors, such as ribosome modulation factor (RMF) and hibernation-promoting factor (HPF) and its homologs, block the mRNA channel and occupy the A- and P-sites of the small ribosomal subunit. Other factors, such as ribosome silencing factor S (RsfS), prevent the association of the 30S ribosomal subunit with the 50S subunit. Recently characterized factors include the paralogous C-tail-anchored membrane proteins YqjD, ElaB, and YgaM, which inactivate ribosomes by blocking the peptide exit tunnel. The coordinated production of these factors is tightly linked to broader stress response pathways, ensuring that ribosomal activity is modulated in accordance with cellular needs. In this review, we describe the diverse mechanisms that bacteria such as E. coli use to silence ribosomes and highlight the flexibility and significance of ribosome hibernation as a conserved strategy for saving energy and for cellular adaptation to stress conditions.