Zhang, Lahry, Cipurko et al. show that the microbial metabolites queuine and preQ1 modify the same host tRNA. PreQ1-tRNA reduces cell proliferation, slows tumour growth, decreases the translation of ribosomal proteins and is cleaved by IRE1 on the ER ribosome.

How m6A in different transcript regions regulates mRNA decay remains an intriguing question. Three studies from the labs of König, Jaffrey, and Steinmetz uncovered translation-dependent CDS-m6A decay: m6A in the coding sequence (CDS) induces ribosome stalling and collision to trigger mRNA decay, while tRNA modification alleviates the effects.

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...

The noncanonical translation initiation factor eIF2A plays critical roles in diverse cellular processes, including the integrated stress response, neurodegeneration and tumorigenesis. However, the precise molecular mechanism underlying eIF2A`s function remains poorly understood. Here, we exploit a TurboID-based proximity labeling combined with mass spectrometry to systematically map the interactome of eIF2A during homeostasis and stress. Combining polysome gradients with TurboID, we zoom into the interactions of eIF2A with the 40S small ribosomal subunit and map the eIF2A binding site close to the mRNA entry channel. We identify a network of interactors that link eIF2A to ribosome-associated quality control, including its strong interaction with G3BP1-USP10 complexes as well as RPS2 and RPS3. In the absence of eIF2A, RPS2 and RPS3 ubiquitination is diminished specifically upon ribosome stalling. 40S-specific footprinting in eIF2A knockout cells shows minimal changes in 5`UTR occupancy, consistent with a limited role for eIF2A in translation initiation. Using dynamic SILAC mass spectrometry, we characterize the novel function of eIF2A in ribosome-associated quality control and show that eIF2A antagonizes USP10-dependent rescue of 40S ribosomes, resulting in altered turnover of 40S subunits upon cellular stress. Collectively, our study identifies a previously unknown link between eIF2A and ribosome-associated quality control, implies that eIF2A promotes translation fidelity by tuning 40S ribosome rescue under stress and warrants further investigations into the role of ribosome-associated quality control in tumorigenesis.

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 ...

Without surveillance, errors in ribosome assembly can lead to the buildup of defective intermediates that impair protein production. Akers et al. developed a system to model faulty ribosomes in human ...

m6A is a potent inducer of ribosome stalling and collisions that trigger YTHDF-mediated mRNA degradation, a process that highlights the ribosome as a critical sensor linking translation dynamics to m6...

Poly(A) tails of newly synthesized mRNAs have uniform lengths, arising through cooperation between the cleavage and polyadenylation complex (CPAC) and poly(A) binding proteins (PABPs). In the budding ...

Ribosome abundance is balanced by production and degradation. Bianco et al. discover that the hibernation factor Stm1 has a dual role in ribosome homeostasis. Stm1 promotes ribosome biogenesis during ...

The ability to study proteins in their native cellular context is crucial to our understanding of biology. In this work, we report a technology for intracellular protein editing, drawing from split in...

In Cancer Cell, two studies unveil mechanisms by which co-option of the protein synthesis machinery promotes cancer progression and potential therapeutic interventions. Kuzuoglu-Ozturk et al. show tha...