Our AI-guided design of RNA-guided nucleases is now out in @science.org 💻🧬 We used structure and evolutionary data to generate minimal, active and divergent gene editors! www.science.org/doi/10.1126/... Congrats to @petrskopintsev.bsky.social @isabelesain.bsky.social @evandeturk.bsky.social & team!

Structure and evolution-guided design of minimal RNA-guided nucleases

The design of RNA-guided nucleases with properties not limited by evolution can expand programmable genome-editing capabilities. However, generating diverse multidomain proteins with robust enzymatic ...

science.org

Out today in @science.org, Doudna lab researchers describe an #AI-assisted method for designing enhanced genome editors, testing close to 2000 in lab. Read more: innovativegenomics.org/news/ai-desi...

AI-Assisted Technique Allows Scientists to Design New, Functional Genome Editors Beyond What Can Be Found in Nature

AI-Assisted Technique Allows Scientists to Design New, Functional Genome Editors Beyond What Can Be Found in Nature - Innovative Genomics Institute (IGI)

innovativegenomics.org

Doudna Lab@doudna-lab.bsky.social · 3w ago

Our AI-guided design of RNA-guided nucleases is now out in @science.org 💻🧬 We used structure and evolutionary data to generate minimal, active and divergent gene editors! www.science.org/doi/10.1126/... Congrats to @petrskopintsev.bsky.social @isabelesain.bsky.social @evandeturk.bsky.social & team!

Our lab is proud to present our latest work harnessing Bridge Recombinase for genome-scale editing in diverse bacteria, microbiome editing, and programmable horizontal gene transfer.

bioRxiv Synthetic Biology@biorxiv-synthbio.bsky.social · 3mo ago

Bridge recombinase enables versatile rewriting of bacterial genomes https://www.biorxiv.org/content/10.64898/2026.04.29.721476v1

Check out this awesome discovery of the RNA-guided VIPR RNP by the Doudna lab. Everything about the system, from its functional context to its targeting code and structural geometry, is truly remarkable. Congrats to the team!

Kenneth Loi@kenjmloi.bsky.social · 3mo ago

Excited to share our discovery of a new programmable RNA-guided DNA-targeting system hiding inside bacteriophages that predates CRISPR. We call it VIPR (Viral Interference Programmable Repeat), and it uses an entirely new logic to find its targets. Thread + link below.

We present VIPR, a phage-encoded RNA-guided system that recognizes DNA with a noncontiguous code unlike CRISPR. Tiny, programmable, possibly ancestral to CRISPR immunity; VIPR is built around a striking RNA-DNA-DNA triplex.

Kenneth Loi@kenjmloi.bsky.social · 3mo ago

Excited to share our discovery of a new programmable RNA-guided DNA-targeting system hiding inside bacteriophages that predates CRISPR. We call it VIPR (Viral Interference Programmable Repeat), and it uses an entirely new logic to find its targets. Thread + link below.

The best thing since *before* sliced bread... VIPRs. www.biorxiv.org/content/10.6... www.biorxiv.org/content/10.6...

Our work investigating mRNA 3' UTRs that trigger target-directed miRNA degradation is now published! genesdev.cshlp.org/content/earl...

David Bartel's Lab@bartellab.bsky.social · 9mo ago

Check out the latest work from our lab, led by Daniel Lin and Lara Elcavage: www.biorxiv.org/content/10.1... (1/3)

MicroRNAs control gene expression by modulating the output and stability of messenger RNAs. How are these crucial regulators kept in check? go.nature.com/4bIecb0

Quirky base pairing attracts rule-breaking enzymes to destroy microRNAs

MicroRNAs control gene expression by modulating the output and stability of messenger RNAs. How are these crucial regulators kept in check?

go.nature.com

Our work on the E3 ligase mechanism of target-directed microRNA degradation is now published! Amazing collaboration with Brenda Schulman’s lab led by @jakobfarnung.bsky.social and @elenaslo.bsky.social, with special thanks to @wyppeter.bsky.social, Lianne Blodgett, and Daniel Lin! tinyurl.com/Z8TDMD

The E3 ubiquitin ligase mechanism specifying targeted microRNA degradation - Nature

Target-directed microRNA degradation is driven by the atypical ZSWIM8–CUL3 E3 ubiquitin ligase that uses a two-RNA-factor authentication mechanism to specifically recognize AGO–miRNA–trigger...

tinyurl.com

David Bartel's Lab@bartellab.bsky.social · 7mo ago

We are thrilled to share our latest work uncovering the mechanistic basis of target-directed microRNA degradation (TDMD). This work was driven by @jakobfarnung.bsky.social and @elenaslo.bsky.social in a fantastic collaboration with Brenda Schulman's lab. tinyurl.com/E3TDMD (1/5)

The E3 ubiquitin ligase mechanism specifying target-directed microRNA degradation (TDMD) is now published! 🎉🍾 We, @bartellab.bsky.social and Schulman lab, describe how 2-RNA factors control protein degradation by recruiting an E3 ligase. @mpibiochem.bsky.social www.nature.com/articles/s41...

🧪🧬New preprint We present cryo-EM structures of reconstituted CTCF–nucleosome complexes, showing CTCF dimerization drives nucleosome oligomerization into defined higher-order assemblies. Disrupting CTCF–CTCF interfaces in mESCs reduces looping and impairs differentiation. tinyurl.com/CTCF-nucleos...

We’re excited to share our latest preprint on the mechanism of excised linear intron stabilization in yeast! This work was led by PhD student @glennli.bsky.social and was a wonderful collaboration with @maxewilkinson.bsky.social. Link: www.biorxiv.org/content/10.6... (1/4)

Check our latest collaboration with the Kleaveland Lab (kleavelandlab.org), led by Joanna Stefano and Lara Elcavage: academic.oup.com/nar/article/... (1/2)

New preprint 👉Doudna x Bryant x Jacobsen x Savage collaboration! Work led by @zehanzhou.bsky.social, I. Saffarian-Deemyad, @honglue.bsky.social, T. Weiss We dissect how stepwise DNA unwinding gates TnpB genome editing, revealing how unwound DNA states enhance cleavage www.biorxiv.org/content/10.6...

Stepwise DNA unwinding gates TnpB genome-editing activity

TnpB is a compact RNA-guided endonuclease and evolutionary ancestor of CRISPR-Cas12 that offers a promising platform for genome engineering. However, the genome-editing activity of TnpBs remains limit...

biorxiv.org

When RNA Degradation 🤝 meets 🤝 Protein Degradation! tinyurl.com/E3TDMD In a collaboration of @bartellab.bsky.social and Schulman lab, we show that, in target-directed microRNA degradation (TDMD), 2-RNA-factors recruit an E3 ligase and induce the degradation of not only a protein but also RNA (1/5).

It's finally the day we unveil this beautiful mechanism + structure of TDMD! It's been a most riveting, collaborative journey with the team. I remember every exciting moment that we revealed a new small piece of the puzzle over the past years, e.g. when we found out that ZSWIM8 would be [1/2]

David Bartel's Lab@bartellab.bsky.social · 7mo ago

We are thrilled to share our latest work uncovering the mechanistic basis of target-directed microRNA degradation (TDMD). This work was driven by @jakobfarnung.bsky.social and @elenaslo.bsky.social in a fantastic collaboration with Brenda Schulman's lab. tinyurl.com/E3TDMD (1/5)

✨New preprint! 🧵1/4 Excited to share our work on AI-guided design of minimal RNA-guided nucleases. Amazing work by @petrskopintsev.bsky.social @isabelesain.bsky.social @evandeturk.bsky.social et al! Multi-lab collaboration @banfieldlab.bsky.social @jhdcate.bsky.social @jacobsenucla.bsky.social🧬 🔗👇

Check out the latest work from our lab, led by Daniel Lin and Lara Elcavage: www.biorxiv.org/content/10.1... (1/3)

mRNA 3′ UTRs direct microRNA degradation to participate in imprinted gene networks and regulate growth

MicroRNAs direct downregulation of target mRNAs. Sometimes, however, this regulatory paradigm inverts, and a target RNA triggers the degradation of a microRNA. This target-directed microRNA degradatio...

biorxiv.org

My first first-author paper is out!🎉 Here we propose a model where a silencing complex, PIWI*, assembles on target RNAs to recruit effectors and shut down transposon activity. Huge thanks to the Brennecke and Plaschka labs, especially Julius and Clemens, and all co-authors!

Julius Brennecke@juliusbrennecke.bsky.social · 11mo ago

PIWI clade Argonautes are essential for transposon silencing. Without them, animals are sterile due to massive transposon activity. But how does piRNA-guided target interaction translate into silencing? PhD student Júlia Portell Montserrat has an intriguing answer www.cell.com/molecular-ce...

Check out the latest work from Jordan Ray (@jordanray.bsky.social), a collaboration between our lab and David Sabatini’s lab. www.biorxiv.org/content/10.1... (1/2)

Lysosomal RNA profiling reveals targeting of specific types of RNAs for degradation

Autophagy targets a wide variety of substrates for degradation within lysosomes. While lysosomes are known to possess RNase activity, the role of lysosomal RNA degradation in post-transcriptional gene...

biorxiv.org

Our work on the function of miR-51/miR-100 is out! miR-100 is widely conserved across eumetazoans but its function has been mysterious. Emilio Santillán found in worms it regulates signaling and extracellular matrix genes, some of which seem to be conserved targets! www.science.org/doi/10.1126/...

An ancient and essential miRNA family controls cellular interaction pathways in C. elegans

A microRNA that arose at the origin of eumetazoans regulates cell adhesion and signaling in C. elegans through conserved targets.

science.org

Argonautes are coming :-) ... soon at @imgprague.bsky.social ... finishing preparations. Still missing a few things like drums, guitar, badges, beer ... but it's under control. I think. I hope. :-)) #argonautes2025

"why [would] anyone intelligent enough to be a scientist choose to be one [given] the unfavorable risk-to-reward ratio "? One of the most intelligent people you could meet offers some answers: having ideas, watching them develop, and sharing them journals.biologists.com/jcs/article/...

Why would anyone want to be a scientist?

It is difficult to fathom why anyone intelligent enough to be a scientist would actually choose to be one. Doing good science requires the utmost exertion of body, mind and spirit, yet is consistently...

journals.biologists.com

Check out the latest study from our lab, led by Coffee Xiang (@coffeebond007.bsky.social) www.nature.com/articles/s41... (1/2)

PAL-AI reveals genetic determinants that control poly(A)-tail length during oocyte maturation, with relevance to human fertility - Nature Communications

Gene regulation in oocytes relies heavily on poly(A) tail-length changes. Here, the authors develop PAL-AI, a neural network model that predicts tail-length changes, identifies regulatory motifs, and ...

nature.com

Beautiful work by Katya Khalizeva from @iaincheeseman.bsky.social lab, uncovering a surprising feedback loop to globally suppress mRNA decay during mitosis! This helps explain how cells maintain their transcriptome during a mitotic arrest without new transcription! www.biorxiv.org/content/10.1...

Global inhibition of deadenylation stabilizes the transcriptome in mitotic cells

In the presence of cell division errors, mammalian cells can pause in mitosis for tens of hours with little to no transcription, while still requiring continued translation for viability. These unique...

biorxiv.org

New preprint! We solve a mystery you didn't know existed. Mitotic cells lack new transcription but require ongoing translation. Interphase mRNA half life is only 2-4 hrs. So how do cells arrest in mitosis for hours without depleting their transcriptomes? www.biorxiv.org/content/10.1...

Global inhibition of deadenylation stabilizes the transcriptome in mitotic cells

In the presence of cell division errors, mammalian cells can pause in mitosis for tens of hours with little to no transcription, while still requiring continued translation for viability. These unique...

biorxiv.org

Nucleic acid structural biologists expose that many CASP16 predictions, even ones obtaining high scores by CASP metrics, are inaccurate in the most functionally relevant regions! Read more insights on functionally relevant features by the expert structure determiners (doi.org/10.1101/2025...).

Functional relevance of CASP16 nucleic acid predictions as evaluated by structure providers

Accurate biomolecular structure prediction enables the prediction of mutational effects, the speculation of function based on predicted structural homology, the analysis of ligand binding modes, exper...

doi.org

AlphaFold is amazing but gives you static structures 🧊 In a fantastic teamwork, @mcagiada.bsky.social and @emilthomasen.bsky.social developed AF2χ to generate conformational ensembles representing side-chain dynamics using AF2 💃 Code: github.com/KULL-Centre/... Colab: github.com/matteo-cagia...

bioRxiv Biophysics@biorxiv-biophys.bsky.social · last yr.

AF2χ: Predicting protein side-chain rotamer distributions with AlphaFold2 https://www.biorxiv.org/content/10.1101/2025.04.16.649219v1

Don’t miss this Q&A with Dr. Michelle Frank (@michelle-frank.bsky.social), an awesome postdoc in our lab!

Whitehead Institute@whiteheadinstitute.bsky.social · last yr.

Our latest Postdoc Q&A features Michelle Frank from the Bartel lab. Michelle is interested in how the brain balances the ability to learn new things with the need for maintaining stable connections. wi.mit.edu/news/meet-wh... #WhiteheadPostdocProfiles @bartellab.bsky.social

What was that you said? You are looking for new #RNA research to read in the weekend? You are in luck! 📣 📣 Check out the new preprint from our lab!!!! 📣 📣 www.biorxiv.org/content/10.1...

AGO2 slicing of a domesticated retrotransposon is necessary for normal vasculature development

Argonaute (AGO) mediated slicing of RNA, also known as RNAi, is a highly conserved phenomenon that is evolutionarily linked to the repression of transposons and other repeats. Although RNAi is no long...

biorxiv.org