Small-molecule modulators of protein synthesis are invaluable tools for dissecting the translation apparatus. This Review summarizes the mechanisms of molecules that disrupt translation in an amino ac...

In eukaryotes, ribosome biogenesis initiates within the nucleolus, a hallmark multilayered compartment of the nucleus. Structures of pre-ribosomes have been characterized ex situ, but their assembly p...

Bacterial ribosomes can synthesize proteins encoded within their own RNA.

Systematic characterization of terminating ribosomes uncovers sequence features influencing ribosome dynamics at stop codons with direct implications in 3' UTR translation.

Mobile genetic elements and their hosts engage in continuous evolutionary conflict. Marino et al. recently uncovered an unusual anti-CRISPR mechanism: the phage protein AcrVA2 triggers translation-coupled mRNA degradation by recognizing nascent Cas12. The findings suggest that nascent peptides may signal an underappreciated layer of gene regulation across the kingdoms of life.

The long-living rodent naked mole-rat has a distinct break in its 28S ribosomal RNA. Here, the authors present cryo-EM structures showing this cleavage is stabilized by surrounding ribosomal proteins,...

The tetracycline class of antibiotics is widely used for treating bacterial diseases including Lyme disease, anthrax, acne vulgaris, and pneumonia. Using a series of high-resolution cryo-electron microscopy (cryo-EM) structures, we show that tetracyclines can simultaneously target the mRNA decoding center in the 30S subunit and the nascent peptide exit tunnel (NPET) in the 50S subunit of the bacterial ribosome. Among the tested tetracyclines, Doxycycline was distinct in its ability to dimerize and bind the NPET at multiple locations. Structural comparison of Doxycycline, Minocycline, and Sarecycline bound to the Escherichia coli and Cutibacterium acnes 70S ribosome revealed species-specific differences affecting drug interaction and occupancy. Our results reveal a dual site mechanism of action for tetracyclines and provide a structural basis for rational design of narrow spectrum tetracyclines to overcome the rising threat of antibiotic resistance. Tetracyclines are among the most wide

How do bacteria regulate the production of their proteins? Researchers at the University of Hamburg, in collaboration with international partners, have now demonstrated how small protein building blocks, known as peptides, specifically influence bacterial protein production.

In this work authors show how minimal mutations in proline-rich antimicrobial peptides can flip their orientation in the ribosome exit tunnel, switching their mechanism from stalling translation termination to halting initiation - revealing a possible host strategy against evolving pathogens.

Atomistic structural ensembles of protein folding intermediates on the ribosome are resolved by comprehensive 19F nuclear magnetic resonance analyses integrated with molecular dynamics simulations, pr...

Abstract. Translation is accompanied by the rotation of the small and large ribosomal subunits relative to each other. Here, we use single-molecule Förster

The common antibiotic doxycycline inhibits the ribosome. Here, using cryo-EM, the authors identify additional binding sites for doxycycline in the Coxiella burnetii and E. coli ribosomes.

In this work authors show how minimal mutations in proline-rich antimicrobial peptides can flip their orientation in the ribosome exit tunnel, switching their mechanism from stalling translation termi...

Improved fractionation strategies can identify antibiotics with previously unseen scaffolds and mechanisms, exemplified by manikomycin from Streptomyces rimosus, which acts by targeting the E-site of ...

Natural products and their derivatives have long served as powerful tools for treating bacterial infections, but the rise of antibiotic resistance thr…

Nature Reviews Molecular Cell Biology - This Review discusses new insights into the intricate regulation of mitochondrial protein synthesis, the pathological consequences of its dysfunction in...

Ribosome arrest peptides undergo programmed translational stalling in response to changes in the cellular environment to feedback-regulate gene expression. CliM, an arrest peptide in Clostridia, is en...

RNase E localization and translation initiation coordinate transcription, translation and mRNA degradation during the life cycle of an mRNA, explaining gene- and species-specific variations in this co...

Abstract. Recently, a tRNATrpCCA with a 4-base-pair (bp) anticodon stem (AS) was shown to efficiently recognize a near-cognate UGA codon in unicellular euk

Abstract. Bacteria of class Bacteroidia lack Shine-Dalgarno (SD) sequences and instead rely on other messenger RNA (mRNA) features, including upstream aden

Pathogenic Bordetella bacteria use protein adhesins to infect the ciliated respiratory epithelia of vertebrate hosts. In this work, we show that the filamentous hemagglutinin FhaB adhesin of Bordetell...

Robust protein synthesis by the ribosome is required for rapid cancer growth. Here authors present interdictors, small molecule inhibitors of protein synthesis with context-dependent activity that inh...

Cells down-regulate protein synthesis when stressed to conserve energy and shift resources toward repair. We found that in some mammalian cells, including neurons, stress also resulted in the formatio...

Abstract The crisis of antimicrobial resistance (AMR) is escalating while the antibiotic pipeline remains stagnant. Our bibliometric analysis of eight decades of literature reveals a critical imbalanc...

Small regulatory RNAs can act on target mRNAs to control their translation and stability. Here, the authors present evidence that this riboregulation can potentially regulate by pairing to a target si...

Large oligomeric proteins constitute a major fraction of proteomes, but are difficult to refold in vitro, raising the question of how cells direct their biogenesis. Roeselová and Shivakumaraswamy et a...

Nature Protocols - This protocol describes inverse toeprinting coupled to next-generation sequencing, an in vitro approach to characterize bacterial translation at codon resolution that can...

The ribosomal exit tunnel is a universally conserved feature of the large subunit that directs the nascent polypeptide chain into the cellular environment and is involved in co-translational folding, ...

Ribosomes translate the genetic code in mRNA to synthesize proteins in all living organisms. Decoding of mRNA occurs in the small subunit of the ribosome and is mediated by tRNA anticodons. Regions ne...

An analysis of AlphaFold protein structure predictions shows that while in many cases the predictions are highly accurate, there are also many instances where the predicted structures or parts of pred...

Tuberculosis is the deadliest bacterial disease on the planet. The months-long regimen of multiple antibiotics required to treat tuberculosis profoundly affects the microbiome and leads to the development of antimicrobial resistance. Furthermore, non-tuberculous mycobacterial infections pose an incr …

Chemical modifications of rRNA, tRNA, and mRNA play key roles in protein synthesis by affecting the structure of these RNAs, by modulating decoding, and by influencing ribosomal efficiency. Recent adv...

Ribosome stalling is a critical regulatory mechanism in protein synthesis, controlling the rate and fidelity of translation. Arrest peptides, short sequences within nascent chains, can induce ribosome stalling, providing insights into the dynamics of translation and potential therapeutic targets. In …