Ribosome collisions activate the ribotoxic stress response mediated by the MAP3K ZAK, which in turn regulates cell-fate consequences through downstream phosphorylation of the MAPKs p38 and JNK1. Despite the critical role of ZAK during cellular stress, a mechanistic and structural understanding of ZAK–ribosome interactions and how these lead to activation remain elusive. Here we combine biochemistry and cryo-electron microscopy to discover distinct ZAK–ribosome interactions required for constitutive recruitment and for activation. We find that upon induction of ribosome collisions, interactions between ZAK and the ribosomal protein RACK1 enable its activation by dimerization of its SAM domains at the collision interface. Furthermore, we discover how this process is negatively regulated by the ribosome-binding protein SERBP1 to prevent constitutive ZAK activation. Characterization of novel SAM variants as well as a known pathogenic variant of the SAM domain of ZAK supports a key role of

Ribosomes—the tiny factories that build proteins in our cells—don't all work with the same efficiency. Researchers from Japan have discovered that ribosomes actually compete with one another, and those that perform poorly are selectively broken down when more efficient ones are present.

Abstract. The N6-methyladenosine (m6A) modification of HIV-1 has been widely studied but the number and precise positions of the m6A sites remain unclear d

Ishiguro et al. identify stereoselective ribose-backbone methylations in the peptidyl-transferase center of E. coli ribosomes, installed by the cobalamin-dependent enzyme RlmX. These methylations, tog...

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

Protein synthesis is precise, with one error per 10,000 incorporated amino acids. This is remarkable, as non-cognate and near-cognate tRNAs (tRNAs that do not match the decoded codon) outnumber…

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During nutrient deprivation, activation of the protein kinase GCN2 regulates cell survival and metabolic homeostasis. In addition to amino acid stress, GCN2 is activated by a variety of cellular stres...

Nature Structural & Molecular Biology, Published online: 19 September 2025; doi:10.1038/s41594-025-01676-5By studying dynamic folding intermediates on the human ribosome, Pellowe et al. show that newly made domains help each other to fold but do not stably interact until synthesis is complete, avoiding interdomain misfolding.

Nature Methods - Translon: a single term for translated regions

When translation elongation is hindered, stalled ribosomes can collide with trailing ribosomes and form ribosome collision complexes also known as disomes. Disomes are sensed in the cell to trigger signaling events, and therefore it is important to determine their frequency and distribution across transcripts. Here, we provide the protocol for Disome-seq in Saccharomyces cerevisiae (yeast) cells to enable transcriptome-wide detection of disomes. We describe the steps for yeast growth and isolati...

tRNAs contain many chemical modifications that regulate their function. Integrating smFRET and cryo-EM approaches, this work demonstrates that m1G37 in tRNAProL stabilizes its conformation in the ribo...

Bimonthly newsletter: RNA modifications and related topics, mostly in bacteria. Summer 2025, first issue!

The C5 methylation of cytidine 1407 (C1407) in the E. coli 16S rRNA is a permanent modification. The methylation occurs directly at the A-site internal loop, a known dynamic hotspot in helix 44 (H44) ...

Translation regulation plays a pivotal role in the diversification of gene expression and the response to intra- and extracellular environmental cues. Ribosome profiling (or Ribo-Seq) serves as a sens...

Sequence and structural analyses reveal a divergent peptidyl transferase centre and a hibernation factor in archaea.

Defining viral proteomes is crucial to understanding viral life cycles and immune recognition but the landscape of translated regions remains unknown for most viruses. We have developed massively para...

Translation termination is essential in all living organisms because it ensures that proteins have lengths strictly defined by their genes. This universal process is mediated by peptide release factor...

Zhang et al. identify a regulatory mechanism for how cells adapt to nutrient scarcity through widespread −1 ribosomal frameshifts, culminating in accelerated mRNA decay. This process, dependent on codon optimality and conserved across species, establishes direct feedback coupling the translation of new proteins with the stability of the mRNA that encodes for them.

Huang et al. identify a pathway for stress-induced 40S ribosome degradation: 40S ribosomes ubiquitylated by RNF10 are subsequently bound by the atypical kinase RIOK3, which mediates their degradation ...

Les cellules utilisent de nombreux mécanismes de contrôle-qualité au cours de la biosynthèse des protéines. Les défauts qui perturbent le décodage de l'ARN messager peuvent provoquer le blocage des ribosomes, empêchant l'expression des gènes. Ces ribosomes bloqués ne sont plus disponibles pour le processus de traduction, ce qui représente un défi à la fois pour l'homéostasie des ribosomes et la survie de la cellule.   Les cellules eucaryotes évitent l'accumulation de polypeptides aberrants potentiellement toxiques et maintiennent la disponibilité des ribosomes en employant des mécanismes de surveillance, comme le complexe de contrôle-qualité associé aux ribosomes (RQC), très conservé au cours de l'évolution. Les voies de sauvetage dissocient le ribosome bloqué, en libérant la sous-unité 40S attachée à l'ARNm et la sous-unité 60S encore attachée à un ARNt avec le peptide en élongation. RQC assure l'ubiquitination, l'extraction et la dégradation du peptide naissant aberrant. En particulier, Rqc2p recrute, à la même position que l’ARNt au site A, des ARNt chargés en alanine et en thréonine, formant des extensions C-terminales composées de ces résidus (CAT-tails). Ces CAT-tails peuvent exposer des résidus lysine cachés dans le tunnel de sortie de la 60S pour l’ubiquitination par la E3 ligase Ltn1.   En utilisant un crible génétique, les scientifiques de l’équipe Génomique, Structure et Traduction à l’I2BC (CNRS/CEA/UPSaclay, Gif-sur-Yvette) ont identifié un allèle mutant de RQC2 comme impliqué dans la libération des peptides à partir des ribosomes bloqués. Ils ont caractérisé la protéine mutante sur le plan biochimique et, en collaboration avec l’équipe de Reynald Gillet (IGDR, Université de Rennes), sur le plan structurel, en déterminant comment la mutation ponctuelle réduisait le recrutement de l'ARNt au site A, limitant ainsi la formation des CAT-tails.   Ces résultats, publiés dans Structure, permettent de mieux comprendre le rôle de Rqc2p dans le complexe de contrôle-qualité associé aux ribosomes, et le maintien de l'homéostasie des ribosomes.   -> Contact : celine.fabret@i2bc.paris-saclay.fr

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Eukaryotic cells prevent the accumulation of potentially toxic aberrant polypeptides and maintain ribosome availability through surveillance and clearance mechanisms, including the evolutionarily cons...

Cells can simultaneously produce structurally dissimilar ribosomes, suggesting functional specialization of distinct ribosome populations. Here, the authors show that distinct ribosomes cooperate rath...

An ancient tRNA modification is used by mammalian cells to coordinate protein translation and adaptive signaling.

Dans une étude publiée dans la revue Nature Communications, des scientifiques révèlent l’existence de nouveaux antigènes produits à partir du génome

Ribosome profiling faces issues with rRNA contamination and measurements of ribosome numbers on transcripts. Here, the authors develop Ribo-FilterOut and Ribo-Calibration, methods which can be used to...

Dual reporters encoding two distinct proteins within the same mRNA have had a crucial role in identifying and characterizing unconventional mechanisms of eukaryotic translation. These mechanisms inclu...