Francesco Scavone

Some molecular machines, like ribosomes, can persist for long periods of time in cells.

Could molecular aging of ribosomes shape how proteins are made?

In our new preprint we track ribosomes as they age in cells and uncover unexpected effects on translation (1/10)

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

I am incredibly excited to share that I will start my independent lab at the @unidue-zmb.bsky.social at the @unidue.bsky.social as Junior Professor of Cellular Biochemistry. Research in my lab has the goal to decipher the ubiquitin code!
There are multiple open positions!
(1/3)

CLCC1 promotes hepatic neutral lipid flux and nuclear pore complex assembly - Nature CRISPR–Cas9 screening identifies CLCC1 as a factor that increases neutral lipid flux to prevent hepatic steatosis and promotes nuclear pore complex assembly by promoting membrane bending and fusi...

Sooo happy to share our new paper in @nature.com “CLCC1 promotes hepatic neutral lipid flux and nuclear pore complex assembly.” A terrific collaboration with @arrudalab.bsky.social, led by co–first authors Alyssa Mathiowetz and Emily Maymand.
www.nature.com/articles/s41...

Really happy to see this one out: www.sciencedirect.com/science/arti... Alibek's drive & great coll w/ friends @gekaragoz.bsky.social & E. Hallacli resulted in a cool story that starts with our beloved #Marchantia and ends with iPSC-derived neurons 🤩🤪 A short 🧵

Quick proteomics question: we want to use an exogenous biotin blocking scavenger for a TurboID experiment. We tried Biolock but is very inconsistent in our hands. Does anyone have another suggestion?

We posted a biorxiv preprint on structural bioinformatics, AlphaFold modeling & machine learning on predicting specificity of E3 ligase ring domains for different E2 enzymes. 1/4

Preprint: www.biorxiv.org/content/10.6...

Models/data (UbiqCore website): dunbrack.fccc.edu/ubiqcore

Mammalian cells form hibernating disomes akin to those in bacterial cells - but connected via ribosomal RNA

www.science.org/doi/10.1126/...

co-first with: @andschwarz.bsky.social

with: @lea-dietrich.bsky.social, @sgiando.bsky.social, @erin-schuman.bsky.social and many more

🧵 0/6
#MolBio 🧪

Ribosomal RNA expansion segments mediate the oligomerization of inactive animal ribosomes Cells down-regulate protein synthesis when stressed to conserve energy and shift resources toward repair. We found that in some mammalian cells, including neurons, stress also resulted in the formatio...

www.science.org/doi/10.1126/...

Such a pleasure to share our commentary on #UFMylation client diversity published in @natrevmcb.nature.com. Thanks to @lisaheinke.bsky.social for the opportunity to write it, reviewers for their peer review contribution, and members of our lab for discussions.
Link: www.nature.com/articles/s41...

New Online! Evaluating evidence for UFMylation client diversity

@hanhtkvu.bsky.social @embl.org & we are looking for a #postdoc to study #regeneration x #autophagy across kingdoms of life. Pls spread the word & get in touch if you are interested www.health-life-sciences.de/opportunitie...

📣 UK Proteostasis Meeting 2026 – Registration Now Open!

I’m delighted to share that registration is now open for the UK Proteostasis Meeting 2026, hosted by The Francis Crick Institute on 20–21 July 2026
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Please register here(lnkd.in/ervXMzWN) and through Eventbrite for payment (lnkd.in/eTxqjnQy)

CSN5i-3 is an orthosteric molecular glue inhibitor of COP9 signalosome - Nature An orthosteric CSN inhibitor gains nanomolar potency via a molecular-glue mechanism, stabilizing a CSN5–N8–inhibitor complex that confers substrate-dependent inhibition despite weak free-enzyme affinity.

Nature research paper: CSN5i-3 is an orthosteric molecular glue inhibitor of COP9 signalosome

go.nature.com/4kwdCRy

STI1 domain engages transient helices to mediate Dsk2 phase separation and proteasome condensation - The EMBO Journal Ubiquitin-binding shuttle proteins are important components of stress-induced biomolecular condensates in cells. Yeast Dsk2 scaffolds proteasome-containing condensates via multivalent interactions wit...

Yeast ubiquilin Dsk2 scaffolds proteasome-containing condensates under stress via multivalent interactions – @castanedalab.bsky.social et al show how dynamic interactions among its STI1 domain & transient helices in its disordered region promote its phase-separation
link.springer.com/article/10.1...

And a new paper from the lab. A follow up to a previous study in which we elucidate the mechanism of the nuclear transport. Read the full story: www.nature.com/articles/s41...

Single-molecule dynamics of the TRiC chaperonin system in vivo - Nature Single-particle tracking experiments in intact cells reveal dynamic co- and post-translational interactions of the TRiC–PFD chaperonin complex with client proteins during in vivo protein folding.

I’m excited to share my first-author paper, with co-first author @rongqinxiaoxiao.bsky.social, now out in @nature.com. We developed a live-cell single-particle tracking platform to see how TRiC & prefoldin engage proteins during co- and post-translational folding. 1/9 www.nature.com/articles/s41...

🚀 Just published: New1 shields mRNAs from no-go decay — by preventing ribosome crashes at specific codons.
What’s new?
New1 (eEF3 homolog) stops ribosomes from stalling at C-terminal AAA/AGG/CGU codons. No New1 = collisions + Hel2 recruitment + Cue2-mediated no-go decay.

Structure of the adaptor protein 4 (AP-4) complex revealed! AP-4 exists in a dynamic equilibrium between closed and open conformations in solution. ARF1 does not shift this equilibrium but is required—together with cargo—for membrane recruitment. rdcu.be/e1ozM

CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis CRISPR screens in iPSC-derived neurons reveal that the E3 ubiquitin ligase CRL5SOCS4 ubiquitinates tau, that CUL5 expression is correlated with resilience in human Alzheimer’s disease, and that electr...

After a long review process, I'm excited that our paper is finally in print: www.cell.com/cell/fulltex...

TL;DR: We use CRISPR screens in iPSC-derived neurons to find a new tau E3 ligase and a relationship between oxidative stress, the proteasome, and tau proteolytic fragments.

More below 👇

Our paper is (finally) out in Cell today!

CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis
www.cell.com/cell/fulltex...

Great collaborative effort - read more from first author @asamelson.bsky.social below:

A very nice #review on #UFMylation from the giants of the field: The mechanistic basis and cellular functions of UFMylation www.nature.com/articles/s41...

The mechanistic basis and cellular functions of UFMylation Nature Reviews Molecular Cell Biology, Published online: 09 January 2026; doi:10.1038/s41580-025-00944-yUFMylation, a ubiquitin-like modification, regulates endoplasmic reticulum-associated ribosome quality control by conjugating UFM1 to the ribosomal subunit RPL26, preserving ribosome integrity under stress. This Review explores the structural basis of UFMylation and its emerging functional breadth, and it discusses putative UFMylation substrates.

New Online! The mechanistic basis and cellular functions of UFMylation

‼️Towards the end of #AusUb25, we caught up with Jonathan Pruneda to discuss ubiquitin signalling and its relationship with host-pathogen interactions. It was an amazing conference and such a great chance to meet people from across the ubiquitin field 🤩

Out in @febsj.bsky.social, comment written with @tonyavril.bsky.social from @csignaling.bsky.social.
https://doi:10.1111/febs.70259
The SARS-CoV-2 spike protein interacts with HAX1 to modulate cellular stress responses through activation of the UPR

Congrats David! Looking forward to read it.

The human ribosome modulates multidomain protein biogenesis by delaying cotranslational domain docking - Nature Structural & Molecular Biology By 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 in...

Our article on human multidomain protein biogenesis is now published in @natsmb.nature.com
www.nature.com/articles/s41...

From MBoC... Dr. Francesco Scavone (Stanford) shows ATG9A has an unexpected role in trafficking K63-polyubiquitin–modified membrane proteins. Blocking the signal traps cargos in vesicle clusters; once released, they rapidly reach lysosomes. 🔗 www.molbiolcell.org/doi/10.1091/... #ASCB #CellBiology

Absolutely honoured to see our work featured on this month’s cover! 🎉🧬

Artwork by the incredibly talented @doroteaartscience.bsky.social 👇

Proud to share what we hope will be a reference study on human oocyte proteostasis. Young-donor eggs show globally reduced organelle activity vs. somatic cells, with an even steeper drop as they mature.
👇 for @zaffagg3 's detailed explanation

www.embopress.org/doi/full/10....

#cryoEM confluence in Munich #womeninSTEM