title: Ribosome hibernation factor promotes Staphylococcal survival and differentially represses translation.
abstract: In opportunistic Gram-positive Staphylococcus aureus, a small protein called hibernation-promoting factor (HPFSa) is sufficient to dimerize 2.5-MDa 70S ribosomes into a translationally inactive 100S complex. Although the 100S dimer is observed in only the stationary phase in Gram-negative gammaproteobacteria, it is ubiquitous throughout all growth phases in S. aureus The biological significance of the 100S ribosome is poorly understood. Here, we reveal an important role of HPFSa in preserving ribosome integrity and poising cells for translational restart, a process that has significant clinical implications for relapsed staphylococcal infections. We found that the hpf null strain is severely impaired in long-term viability concomitant with a dramatic loss of intact ribosomes. Genome-wide ribosome profiling shows that eliminating HPFSa drastically increased ribosome occupancy at the 5' end of specific mRNAs under nutrient-limited conditions, suggesting that HPFSa may suppress translation initiation. The protective function of HPFSa on ribosomes resides at the N-terminal conserved basic residues and the extended C-terminal segment, which are critical for dimerization and ribosome binding, respectively. These data provide significant insight into the functional consequences of 100S ribosome loss for protein synthesis and stress adaptation.
authors.affiliation: Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
authors.forename: Arnab
authors.initials: A
authors.lastname: Basu
authors.affiliation: Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA myap1@slu.edu.
authors.forename: Mee-Ngan F
authors.initials: MN
authors.lastname: Yap
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D018387:Codon, Initiator; D019281:Dimerization; D050296:Microbial Viability; D016296:Mutagenesis; D009154:Mutation; D014176:Protein Biosynthesis; D012269:Ribosomal Proteins / Q000235:genetics / Q000502:physiology*; D012270:Ribosomes / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000235:genetics* / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D018387:Codon, Initiator; D012269:Ribosomal Proteins