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…

Issue #5

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...