Ribosome recycling’s role in translational regulation remains unclear. Miluzio, Scagliola, et al. show that blocking eIF6 phosphorylation by environmental stressors delays ribosome recycling at stop codons, leading to translational reprogramming and establishing RESt. RESt is reversible, characterized by metabolic remodeling, low translation, reduced reinitiation, and NF-κB pathway activation.

Francisella tularensis is the causative agent of tularemia, a zoonotic disease named after the city of Tulare, California. Symptoms include sudden fever, chills, fatigue, and swollen lymph nodes, among others, and without treatment it is very serious or even fatal. In addition, F. tularensis is considered a potential bioterrorism threat due to its high infectivity and lethality. Ribosomes are key targets for many classes of antibiotics. In this study, we examined the F. tularensis ribosome and determined its structure at 2.5A resolution using cryo-electron microscopy. Notably, we observed the stress-induced ribosome-associated inhibitor A (RaiA) protein bound to the ribosome. RaiA functions as a molecular hibernation factor, inhibiting bacterial translation in response to stress or nutrient deprivation. This mechanism parallels that described in the model organism Escherichia coli and in several pathogenic bacteria, such as Staphylococcus aureus. Furthermore, we solved structures of the antibiotics chloramphenicol and gentamicin bound to the F. tularensis ribosome. Collectively, these results provide structural insights that highlight previously unexplored opportunities for therapeutic intervention.

Inspired by the advance in protein structure prediction, CryoAtom builds protein models directly from cryogenic electron microscopy maps, producing more complete models, reducing the resolution requir...

RNA repair helps bacteria survive antibiotic stress. Here, authors show that Rtc-driven repair causes cell-to-cell variation in resistance levels, revealing a potential form of heteroresistance, and identify key Rtc targets to enhance antibiotic effectiveness.