npj Antimicrobials and Resistance - Predicting drug inactivation by changes in bacterial growth dynamics

Nanopore direct RNA sequencing promises to decode the epitranscriptome by detecting multiple modifications on individual RNA molecules, but its potential for biological discovery is hampered by high f...

A two-component system, DbfRS, regulates biofilm formation in Vibrio cholerae. Here, Nguyen et al. identify a small periplasmic protein that controls the activity of the system’s receptor, and show th...

Abstract. Polymorphic toxin systems (PTS) are widespread and play an important role in bacterial competition and shaping communities. However, these system

Abstract. Double-stranded DNA ends arise from external agents or cellular processes like transcription–replication collisions (TRCs), threatening genome st

Abstract. Protein synthesis efficiency is highly dependent on the messenger RNA (mRNA) coding sequence. Furthermore, there is extensive evidence of a corre

Bacterial biofilms include viscous extracellular polymeric matrices such as extracellular DNA (eDNA). Here, Mugunthan et al. show that protein RecA generates three-stranded nucleic acid structures kno...

Abstract. RNA modifications play a fundamental role in regulating essential cellular processes, including translation fidelity and stress adaptation. While

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Abstract. Peptide deformylases (PDFs) are enzymes that are essential for bacterial viability and attractive targets for antibiotic development. Yet, despit

issue no. 6

Decades of research into the noncoding transcriptome have unveiled a complex, multilayered web of molecular interactions that govern gene expression, protein synthesis, and cellular function, challeng...

Abstract. Peptide deformylases (PDFs) are enzymes that are essential for bacterial viability and attractive targets for antibiotic development. Yet, despit

SAR11 bacteria and their phages are abundant in the oceans. Here the authors quantify the number of phage-infected SAR11 cells using microscopy techniques and discover phage-infected cells without any...

by Leah E. Escalante, James Hose, Jamie M. Ahrens, Hollis Howe, Norah Paulsen, Sofia J. Liss, Michael Place, Audrey P. Gasch Down syndrome, caused by an extra copy of Chromosome 21, causes lifelong problems. One of the most common phenotypes among people with Down syndrome is premature aging, including early tissue decline, neurodegeneration, and shortened life span. Yet the reasons for premature systemic aging are a mystery and difficult to study in humans. Here we show that chromosome amplification in wild yeast also produces premature aging and shortens life span. Chromosome duplication disrupts nutrient-induced cell-cycle arrest, entry into quiescence, and cellular health during chronological aging, across genetic background and independent of which chromosome is amplified. Using a genomic screen, we discovered that these defects are due in part to aneuploidy-induced dysfunction in Ribosome Quality Control (RQC). We show that aneuploids entering quiescence display aberrant ribosome profiles, accumulate RQC intermediates, and harbor an increased load of protein aggregates compared to euploid cells. Although they maintain proteasome activity, aneuploids also show signs of ubiquitin dysregulation and sequestration into foci. Remarkably, inducing ribosome stalling in euploids produces similar aging phenotypes, while up-regulating limiting RQC subunits or poly-ubiquitin alleviates many of the aneuploid defects. We propose that the increased translational load caused by having too many mRNAs accelerates a decline in translational fidelity, contributing to premature aging.

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.

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.