Alessandro Scacchetti

A retroelement-derived mammalian ARC protein exhibits selective RNA recognition and nucleic acid chaperone functions - PubMed Activity-regulated cytoskeleton-associated protein (ARC) is an RNA-binding protein that also serves as a central hub for neuronal protein-protein interactions. It is essential for intercellular signaling and contributes to synaptic plasticity. ARC includes Gag-like sequences of Ty3/Gypsy retrotransp …

#TEsky A retroelement-derived mammalian ARC protein exhibits selective RNA recognition and nucleic acid chaperone functions pubmed.ncbi.nlm.nih.gov/41797537/

YESS Charles Leclerc
!! A podium to kick off 2026! 🏆

Deltaviruses spread through a viral Trojan Horse Hepatitis D-like satellite viruses, known as deltaviruses, have been recently discovered in a wide range of animals. These viruses are thought to expr…

We found a viral Trojan Horse: a virus can hide inside another virus.This one surprised us: deltaviruses don’t just borrow a helper virus. They can travel inside it.
A literal Trojan Horse “virus-in-a-virus” route into cells. 🤯 Kudos to 1st author @viroscope.bsky.social and co-authors !

Pseudouridine selects RNAs for extracellular transport www.biorxiv.org/content/10.1...

Also, I am moving back to Europe and I'm looking for a job :)

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I’d like to thank everyone involved—labmates, collaborators, and especially Roberto, who gave me the opportunity to pursue this “wild” project and supported me every step of the way.

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The genetic identification and biochemical validation of this and other mechanisms governing exRNA selection will help uncover the biological functions of extracellular RNAs and ultimately decode the language of RNA-mediated cell-to-cell communication.

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In summary, we uncover a pathway for RNA secretion, whereby PUS1 catalyzes the formation of Ψ on select RNAs, marking them for export through recognition by MYL6.

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So how might Ψ drive exRNA export?

One possibility is that RNA-binding proteins recognize Ψ-marked RNAs and channel them into secretory pathways.

Surprisingly, we found that MYL6 (myosin light chain 6) selectively binds Ψ-containing exRNAs and is required for their extracellular transport.

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But is Ψ also necessary?

PUS1 depletion causes loss of Ψ at hundreds of RNA sites. Importantly, export of RNAs carrying PUS1-dependent Ψ is the most strongly affected.

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Interestingly, Ψ appears sufficient to promote secretion, at least when introduced into synthetic RNAs.

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Because PUS1 is required for the release of some exRNAs, we hypothesized that its catalytic product (Ψ) might promote RNA export.

By adapting LIDAR to detect Ψ genome-wide, we found that exRNAs carry higher levels of Ψ than intracellular RNAs, suggesting a link with secretion.

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When we depleted PUS1, exRNA export was dramatically altered.

Pseudouridine guides germline small RNA transport and epigenetic inheritance - Nature Structural & Molecular Biology Germline small RNAs in plants and mammals are marked by pseudouridine. In plants, Exportin-t is required for pseudouridylation, transport and localization of small RNAs in pollen, as well as for epige...

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We focused on the pseudouridine (Ψ) synthase PUS1. It was among the top hits, and genetic evidence implicates Ψ in RNA mobility in A. thaliana pollen:
www.nature.com/articles/s41...

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Two classes of hits stood out:

• RNA modifiers, linking chemical RNA modification to secretion
• Domesticated retroviral proteins, suggesting that some RNAs may be exported in virus-like particles (tinyurl.com/5n7jsfp2)

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To identify regulators of neuronal exRNA export, we devised a genome-wide CRISPR screening strategy in which secreted sgRNAs link each cell’s genotype to its extracellular RNA phenotype.

The screen revealed thousands of potential exRNA regulators.

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But first, what are these exRNAs?

Using LIDAR (tinyurl.com/jcutkc8h), a technique we developed to sequence all kinds of RNAs, we identified thousands of RNAs enriched outside our model neuronal cell line (CAD) and in primary neurons.

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So we started from the basics:

How do cells, and particularly neurons, decide which RNAs are exported outside?

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We know very little about the function of extracellular RNAs (#exRNAs), especially in the context of brain biology.

And even at a more fundamental level, the mechanistic rules governing mammalian exRNA trafficking remain largely obscure.

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RNAs usually travel through the extracellular space packaged in structures known as extracellular vesicles (EVs), although other types of RNA-containing particles have also been described.

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Across the kingdoms of life, cell-to-cell RNA communication appears to regulate important biological processes, including host–pathogen interactions, epigenetic inheritance, and behavior.

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Almost every cell you can think of secretes RNAs, including neurons.

But how are specific RNA molecules selected for extracellular export?

We set out to address this question in our latest preprint: www.biorxiv.org/content/10.1...

A long-overdue thread 🧵

Lots of very good papers so far in 2026, but this is one of my favorites:

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

Stability of epigenetic transgenerational inheritance of adult-onset disease and parturition abnormalities | PNAS www.pnas.org/doi/10.1073/...

The study finds 20 generations of epigenetic effects follow exposure of rats to the fungicide vinclozolin. It's likely to provoke vigorous debates.

Please check out our latest #preprint to study #ACTIVELY TRANSLATING #tRNA populations and their dynamics upon #stress :) This was an wonderful collaborative effort between @novoalab.bsky.social @immagina.bsky.social and #Soares teams - thank you for making this possible!

Defining the reference proteomes for small extracellular vesicles and non-vesicular components - Nature Cell Biology Morales-Sanfrutos, Etxeberria-Ugartemendia, Barroso-Gomila and colleagues map the elution profiles of small extracellular vesicles along density gradients from human biofluids and cell lines, distingu...

☕Morales-Sanfrutos, Etxeberria-Ugartemendia, Barroso-Gomila et al map the elution profiles of small #ExtracellularVesicles along density gradients from human biofluids and cell lines, distinguishing extracellular vesicle content from co-isolation components.
bit.ly/3ZWmeHJ

Dosage compensation defects due to roX RNA deletion are rescued by recalibration of X/autosome stoichiometry https://www.biorxiv.org/content/10.64898/2026.02.24.707606v1

Pleased to share the final version of this behemoth of a paper, now finally published. I guess I can retire now?
www.nature.com/articles/s41...

More functional data, many thousands of words removed, and a few other updates from last year's preprint.

Nice!

ADAM10 tailors extracellular vesicles for content transfer rather than signaling by contact https://www.biorxiv.org/content/10.64898/2026.02.12.705562v1