New preprint from
@novoalab.bsky.social !

Which tRNAs are used by ribosomes during translation?

We introduce tRIBO-seq, a nanopore method to sequence ribosome-associated tRNAs and track how the active tRNA pool changes across stress conditions.

www.biorxiv.org/content/10.6...

Thread 👇

In this review, we highlight the recent innovations that have expanded the utility of ribosome profiling (Ribo-seq) to resolve distinct ribosome populations, and how these approaches advanced our understanding of translational control bit.ly/4p4aY6h

ZAK activation at the collided ribosome | Nature 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

Ribosome collisions activate ZAK, influencing cell fate via p38 & JNK phosphorylation. Biochemistry & cryo-EM uncover distinct ZAK-ribosome interactions. PMID:41261136, Nature 2025, @Nature https://doi.org/10.1038/s41586-025-09772-8 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Mechanistic model for +1 frameshifting suppression. The m¹G37 tRNA modification blocks expanded codon–anticodon interactions, preserving translational fidelity.

A (belated!) highlight from an excellent collaboration with
@dunhamlab.bsky.social and #HouLabTJU.

In this Nat Commun paper, we combine smFRET and cryo-EM to show how the tRNA modification m¹G37 stabilizes the reading frame—and what happens when it’s missing.

Cells reveal 'survival of the fittest' through ribosome competition 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.

Cells maintain protein synthesis quality by allowing more efficient ribosomes to outcompete and trigger the removal of less efficient ones, supporting cellular accuracy and resilience.

In this article we provide a high-resolution view of the HIV-1 m6A landscape using direct RNA sequencing approach. We discovered new m6A sites specific from viral mRNA isoforms. So much remains to be done to understand their roles and why they are clustered like this on the HIV genome.

High-resolution HIV-1 m6A epitranscriptome reveals isoform-dependent methylation clusters and unique 2-LTR transcript modifications 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

I am very pleased to share our latest article published in NAR Genomics and Bioinformatics. A collaborative effort with great colleagues from the I2BC NGS facility.

thanks to @i2bcparissaclay.bsky.social for its financial support through epiRNA programs

academic.oup.com/nargab/artic...

Hypoxia-induced ribosomal RNA modifications in the peptidyl-transferase center contribute to anaerobic growth of bacteria 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...

This is a very interesting reaction catalyzed by a radical SAM enzyme on the ribosome (plus uses methyl cobalamin).

Hypoxia-induced ribosomal RNA modifications in the peptidyl-transferase center contribute to anaerobic growth of bacteria: Molecular Cell www.cell.com/molecular-ce...

Thank you Vicky !

Over the weekend, Molecular Genetics and Genomics published our most recent paper.

Upstream start codons can produce alternative proteins with novel N-terminal amino acids that block signal peptides.

These proteins are translated but not found in any proteomics experiments.

rdcu.be/eUi7o

Beyond RNA modification: a novel role for tRNA modifying enzyme in oxidative stress response and metabolism Abstract. RNA modifications play a fundamental role in regulating essential cellular processes, including translation fidelity and stress adaptation. While

Our new paper on DusB’s role in redox metabolism in V. cholerae is now out in @narjournal.bsky.social linking tRNAmodif enzymes and metabolic adaptation.

Beyond RNA modification: a tRNA-modifying enzyme shaping oxidative stress resilience and metabolism in V. cholerae #rnasky #rnabiology

😊🦠💫

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I would be curious to see cryoEM of such translational ribosomes. Could change our way to see translation if true. However this seems so infeasible for the ribosome to translate in the opposite direction.. 🤔

tRNA selection in eukaryotes: A new twist in a familiar tale 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…

In the New and Notable "tRNA selection in eukaryotes: A new twist in a familiar tale," Moumita Dey and Alexey Petrov highlight the paper "Near-Cognate tRNAs Enhance tRNA Rejection and Prime the Ribosome for Rapid Subsequent tRNA Testing."

Using "in extracto cryo-EM", we visualize ribosomes in mammalian lysates, including RRL. "Hibernating" ribosomes carry an extended set of proteins that protect functional centers. These include elongation factor eEF2, LARP1 implicated in mTOR signaling, eIF5A etc. www.biorxiv.org/content/10.1...

Waouh translational termination depends on circadian cycle!

Leoš Valášek, Julius Lukeš, Olivier Namy (@onamy.bsky.social) and Mark Osborn are among the winners of 2025 Synergy Grants.

They'll investigate premature termination codons, the genetic 'stop signals' that cut production of proteins short causing disorders. 🧬🔬

👉 buff.ly/ZQhLp4h

#ERCSyG

Thank you Daniel

Thank you Vicky

I am very proud to announce that our team has received an ERC synergy grant from @erc.europa.eu. A wonderful recognition of a truly collaborative effort with friends (Julius Lukes, Leos Valasek and Mark Osborn). Excited to begin this journey at @i2bcparissaclay.bsky.social @cnrs.fr

Thank you Alexis.

📰 🎃 RNA Modifications Newsletter – October 31st - November 1st, 2025 Issue #5

🎃 Trick or transcript?
Bacteria rewire their RNA world under stress & infection. tRNA mods as dual-function sensors, phage tRNA slashers, hibernating ribosomes & haunted translation hubs.
🧬🧪 Full November 1st issue → #RNAmod #Epitranscriptomics #HalloweenScience
#rnasky #microsky

Excited to announce the YAK lab's first paper and the discovery of the FIRST human cellular PRF signal to give access to two overlapping open reading frames (science.org/doi/10.1126/...)! Before we dive in, the story actually begins in a Nature from 11 years ago

Pelota, a ribosome rescue factor, unlocks the secret to longevity and age-defying health across species. This discovery sheds light on how quality control in protein synthesis can combat ...

🧵 Thread below

Full analysis: helixbrief.com/article/a2e1736b-7031-4c...

Probably one of the best European lab if you are interested in ribosome structure! Go go go

Great work! What is the proportion of ribosomes bound to hib? Does it translocate like tRNAs? Or directly binds each ribosomal sites?

A new family of ribosome hibernation factors in Archaea www.biorxiv.org/content/10.1101/2025.10....

GCN1 couples GCN2 to ribosomal state to initiate amino acid response pathway signaling 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...

Beautiful reconstitution of amino acid stress-dependent ISR activation by my @harvardcellbio.bsky.social colleagues presenting a unifying mechanism for GCN2 activation, which requires ribosome collisions and is enhanced by cognate uncharged tRNA in the A site! www.science.org/doi/10.1126/...

The human ribosome modulates multidomain protein biogenesis by delaying cotranslational domain docking 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.

New online: The human ribosome modulates multidomain protein biogenesis by delaying cotranslational domain docking