Hibernation-Promoting Factor Sequesters Staphylococcus aureus Ribosomes to Antagonize RNase R-Mediated Nucleolytic Degradation

Abstract

Ribosome hibernation is pivotal for the rapid recovery of translation after quiescence in both bacteria and eukaryotes. Ribosome hibernation factors sterically occlude the entry of mRNA and tRNA and are thought to primarily maintain ribosomes in a translation-repressive state, thereby providing a pool of readily recyclable 70S or 80S complexes upon dissociation of the hibernation factors.

Absence of Ribosome Modulation Factor Alters Growth and Competitive Fitness of Escherichia coli

“…Ribosome hibernation and inactivation are phenomena that occur in E. coli as a response to stress and low-nutrient conditions ( 1 – 6 ). Several roles for this have been proposed, including ribosome preservation and preparation of cells for the reinitiation of growth upon reinoculation into rich medium ( 6 , 25 , 31 , 35 ). In E. coli , the dimerization of two 70S ribosomes requires the participation of RMF and HPF, while the binding of YfiA leads to inhibition of translation ( 6 ).…”

“…Another Gram-negative bacterium, Pseudomonas aeruginosa , also exhibited increased ribosomal degradation when HPF, a protein involved in hibernation, was absent ( 30 ). This phenomenon also occurred in Gram-positive bacteria, which displayed increased ribosomal degradation during hibernation when deficient in the long form of HPF, the sole hibernation protein in these Gram-positive microbes ( 25 , 31 ). In addition, Yamagishi et al reported a loss of viability in rmf mutant cells after 4 days in batch culture ( 4 ).…”

“…Through the first two phases, RMF levels remain relatively low until cells transition into stationary phase. During this time, 100S ribosomes form and have been reported to be responsible for modulating the rate of ribosomal degradation that occurs during the entry into stationary phase ( 22 – 25 ). This ribosomal degradation in stationary phase can be visualized by observing cells stained with acridine orange ( 26 ).…”

Coordination of CcpA and CodY regulators in Staphylococcus aureus USA300 strains

“…HPF is a small peptide that dimerizes 70S ribosomal subunits to form inactive 100S subunits 33,34 . It plays an important role in stress response, nutrition limitation and protects ribosomal pools from degradation [35][36][37] . Previous studies in S. aureus have shown that SigB and CodY regulate hpf expression in response to heat and nutritional stress 35 .…”

Ribosomal Hibernation-Associated Factors in Escherichia coli

“…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]. Although these results include cases of specific species except for gammaproteobacteria, the inter-subunit proteins of non-active ribosomes may typically protect the machinery from degradation under stress conditions.…”