Ribosome remodeling drives translation adaptation during viral infection and cellular stress https://www.biorxiv.org/content/10.1101/2025.10.24.684008v1

Oxidative stress sensing by the translation elongation machinery promotes production of detoxifying selenoproteins Selenocysteine, incorporated into polypeptides at recoded termination codons, plays an essential role in redox biology. Using GPX1 and GPX4, selenoenzymes that mitigate oxidative stress, as reporters,...

Colliding ribosomes are potent signals of cellular stress. But do cells use ‘programmed’ ribosome collisions to regulate gene expression? I’m excited to present a new story from my lab led by Frederick Rehfeld(@fred-rehfeld.bsky.social) which revealed that the answer is YES! Read on to find out how👇

Two microbiome metabolites compete for tRNA modification to impact mammalian cell proliferation and translation quality control - Nature Cell Biology 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.

☕Pan, David, Chevrier & co show that the microbial #metabolites queuine and preQ1 modify the same host tRNA. PreQ1-tRNA reduces cell proliferation, slows #tumor growth, decreases the translation of ribosomal proteins and is cleaved by IRE1 on the ER #ribosome.
👉https://rdcu.be/eJqFc
bit.ly/46BPXtJ

Nothing like a coffee break to fuel great conversations ☕✨ Our #EMBLProtein participants are connecting and recharging after the first half of session 1 'Ribosome, elongation, and termination'.

Starting Session 2 'Quality control' strong!

🎙️Oliver Mühlemann opens with 'Deciphering the role of the deubiquitinase USP9X in ribosome-associated quality control' at #EMBLProtein.

We’re back! 🥳

Kicking off our first conference after the summer break: 'Protein synthesis and translational control'.

🌟Today’s highlights include keynote lectures from Lori Passmore, Reuven Agami, and Marina Rodnina.

Welcome to #EMBLProtein! 🎉

Finally out!
I’m thrilled to share our new paper (Wolin et al., Cell 2025).

This paper describes SPIDR, a high-throughput method for mapping RBP binding sites.

By combining #SPIDR with #cryoEM, we identified the exact binding site of LARP1 within the #mRNA channel of the 40S ribosomal subunit.

m6A-induced ribosome stalling and collision trigger mRNA decay 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.

m6A-induced ribosome stalling and collision trigger mRNA decay

📣 Online now - the Review "The ribosome ubiquitination code: fine-tuning translation under stress" from
Haleigh Wooters, Neil Nimmagadda, Alicia Darnell, and @thesilvalab.bsky.social .

#Ubiquitination #TranslationalReprogramming #StressResponse

Read it here: authors.elsevier.com/a/1lPPS3S6Gf...

New paper out in Mol Cell, where we show how N-myristolytransferases lipidate proteins on the translating ribosome!
Continuing our successful collaboration with DeuerlingLab @uni-konstanz.de & Shu-ou Chan @caltech.edu
@snsf.ch @ethz.ch
www.cell.com/molecular-ce...

Pan-viral ORFs discovery using massively parallel ribosome profiling 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...

With the help of a technique called Massively Parallel Ribosome Profiling, researchers in Science have identified more than 4000 open reading frames—stretches of genetic material that can encode proteins—across 679 human-associated viral genomes. scim.ag/43RoAdF

Mechanism of release factor–mediated peptidyl-tRNA hydrolysis on the ribosome 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...

www.science.org/doi/10.1126/... le 🦠💫💫💫 #ribosome #rnasky

We are happy to share that our snR30 story is finally out in @natureportfolio.nature.com 🥳 We report the first structure of a H/ACA snoRNP acting in ribosome synthesis thereby providing a detailed structural and biochemical view of the snR30 snoRNP guiding local 18S rRNA subdomain folding. 👇👇👇

Poster: EMBO Workshop. Ribosome Synthesis: From Mechanisms to Therapy 13th Edition. Churchill College, Cambridge, UK. Sunday 7th-Friday 12th September 2025. EMBO-funded event.

This September, join the EMBO Workshop at Churchill College in Cambridge, hosted by an EMBO organising committee including our Affiliate PI Professor Alan Warren.

Abstracts to present are due 12 June, and registration closes 22 August.

Find more info here: tinyurl.com/ribosomesynt...

The alternative initiation factor eIF2A regulates 40S subunit turnover in ribosome-associated quality control 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.

(BioRxiv All) The alternative initiation factor eIF2A regulates 40S subunit turnover in ribosome-associated quality control: The noncanonical translation initiation factor eIF2A plays critical roles in diverse cellular processes, including the integrated stress response,… #BioRxiv #MassSpecRSS

Ribosomes modulate transcriptome abundance via generalized frameshift and out-of-frame mRNA decay 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.

Ribosomes modulate transcriptome abundance via generalized frameshift and out-of-frame mRNA decay

RIOK3 mediates the degradation of 40S ribosomes 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 ...

RIOK3 mediates the degradation of 40S ribosomes: Molecular Cell www.cell.com/molecular-ce...

ZNF574 is a quality control factor for defective ribosome biogenesis intermediates 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 ...

ZNF574 is a quality control factor for defective ribosome biogenesis intermediates: Molecular Cell www.cell.com/molecular-ce...

A Review from experts in cryo-EM and X-ray crystallography describes the latest and greatest strategies for time-resolved structural biology.

www.nature.com/articles/s41...

m6A alters ribosome dynamics to initiate mRNA degradation 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...

Ribosome collisions and stalling senses m6A presence in mRNA which then starts degradation of m6A-containing mRNA.

www.cell.com/cell/abstrac...

A kinetic ruler controls mRNA poly(A) tail length 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 ...

New work from Matti Turtola showing that mRNA poly(A) tail length is controlled by a kinetic ruler. A real pleasure to work with him!
www.biorxiv.org/content/10.1...

Stm1 regulates Ifh1 activity revealing crosstalk between ribosome biogenesis and ribosome dormancy 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 ...

Stm1 regulates Ifh1 activity revealing crosstalk between ribosome biogenesis and ribosome dormancy: Molecular Cell www.cell.com/molecular-ce...

Intracellular protein editing enables incorporation of noncanonical residues in endogenous proteins 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...

Intracellular protein editing enables incorporation of noncanonical residues in endogenous proteins | Science www.science.org/doi/10.1126/...

Excited to share new research led by our very own @lingdong-shi.bsky.social showing that many archaeal 23S rRNAs are circularized in active ribosomes. Check out the preprint below.

🧬🦠🧫 @science.org RNA-mediated CRISPR-Cas13 inhibition through crRNA structural mimicry | Science www.science.org/doi/10.1126/... meeskelab.org bit.ly/sustecheducnJiaLab #CRISPR #RNA

There is one day left before early bird registration closes for the Ribosome Synthesis meeting in Cambridge, UK, on September 7-12, 2025. Great lineup of speakers. Generous child care grants are available for attendees. Check under the 'Funding' tab.

www.eventsforce.net/hg3/frontend...

Ribosomal rebellion: When protein factories drive cancer progression 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...

Ribosomal rebellion: When protein factories drive cancer progression: Cancer Cell www.cell.com/cancer-cell/...

One more week for early bird registration deadline to the Ribosome Synthesis conference in Cambridge UK September 7-12 2025. Incredible lineup of speakers. Register at
www.eventsforce.net/hg3/frontend...

The cover of the April issue of @cp-trendspharma.bsky.social. Gregory Howard and William Tansey review the current status, challenges, and future prospects of cancer treatments that target the ribosome. Aberrant ribosome production and function are hallmarks of cancer.

Highly conserved ribosome biogenesis pathways between human and yeast revealed by the MDN1-NLE1 interaction and NLE1 containing pre-60S subunits pubmed.ncbi.nlm.nih.gov/40207627/ #cryoEM