How do you get a charged drug into a cell when charged molecules can't cross the membrane? You don't — you let the cell do the charging. Check our new paper "Charged molecular glue discovery enabled by targeted degron display" in Nature Chemical Biology.
❕Publication: www.nature.com/articles/s41...
Excited to share our work on the structure and function of cytoplasmic lattices within mouse embryos. A collaborative effort with @niakanlab.bsky.social and work led by @kashishsingh.bsky.social and @inaharasimov.bsky.social . It is now out on BioRxiv: www.biorxiv.org/content/10.6...
Excited to decode the intricate language of ubiquitin chains and unravel their role in protein degradation? 🧬🔬
👉 APPLY NOW to join the lab of Dr. Leo Kiss @leokiss.bsky.social @imprs-lm.bsky.social.
#CellularBiochemistry #Ubiquitin #Proteostasis #ProteinDegradation
The E3 ubiquitin ligase mechanism specifying targeted microRNA degradation pubmed.ncbi.nlm.nih.gov/41851464/ #cryoEM
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
Thank you Leo!
Glückwunsch, Bruderherz! Really outstanding work by @bartellab.bsky.social and Schulman Lab. This is how transatlantic research is done 🇺🇸🇩🇪.
🎉🎉 @elenaslo.bsky.social 🎉🎉 deserves a special shut-out. She kick-started this project, established a bunch of assays, taught us so many things about miRNA biology and overall has been an amazing colleague to work with!
Just like RNA and protein degradation collaborating in TDMD this work was also a great collaboration of Bartel and Schulman lab. @elenaslo.bsky.social @wyppeter.bsky.social , Daniel Lin, Lianne Blodgett.
Our structure showed that ZSWIM8 positively selects for CUL3 by tightly binding to CUL3’s N-terminal tail. It also selects against other cullins using a ZSWIM-family specific insertion.
One of the surprising findings of the original identification of ZSWIM8 was the identification of CUL3 as its E3 partner. ZSWIM8 forms a complex with ELOB/C and would be expected to interact with CUL2 or CUL5 instead. Reconstitution of TDMD confirmed that ZSWIM8, indeed, interacts with CUL3.
But why does ZSWIM8 require such a recognition mode? Trigger-bound AGO complexes are sparse in cells compared to the thousands of other AGO complexes that shouldn’t be targeted by ZSWIM8. So, miRNA and trigger function as a 2-RNA factor authentication mechanism that licenses AGO for degradation.
Trigger RNA also affects the trajectory of the miRNA-trigger duplex due to a central bulge of unpaired bases. The duplex is ⤴️ redirected placing it in the perfect position to interact with ZSWIM8. Flanking regions of the trigger RNA extending beyond the base pairing bases embrace the ZSWIM8 dimer 🫂
The trigger RNA shows extended base-pairing with the 3’-region of the miRNA removing the miRNA from binding the PAZ domain. The PAZ domain rotates allowing ZSWIM8 to detect the presence of an miRNA-free PAZ domain.
How does ZSWIM8 distinguish trigger-bound AGO complexes from all the other AGO complex? The trigger RNA has a unique base-pairing pattern with the miRNA which induces unique conformational changes of both AGO and the RNAs themselves. ZSWIM8 recognizes every single one of these changes.
Using cryo-EM❄️🔬 we showed that ZSWIM8 forms a dimeric clamp that engulfs the entire AGO–miRNA–trigger RNA complex using both RNA and protein interactions. ZSWIM8-CRL3 selectively ubiquitylates AGO only when bound to trigger RNA and induces its degradation and exposure of miRNA to cellular nucleases.
Usually, miRNAs partner with AGO and repress the mRNAs. TDMD is a reversal of this process in which a RNA called “trigger” causes degradation of the miRNA instead. Beautiful work by the Bartel and Mendell labs showed that TDMD requires the UB activity of the orphan CRL substrate receptor ZSWIM8.
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...
Excited to announce that FASEB Ignite Career Forum 2026 (preceding FASEB Ubiquitin Mechanisms, Functions, and Therapeutics & Protein Folding in the Cell) is open for registration! Abstract deadline - April 6, 2026
For more details -
events.faseb.org/event/Protei...
events.faseb.org/event/Ubiqui...
Congratulations, @leokiss.bsky.social ! 🎉🎉 looking forward to the exciting research of the Kiss lab. This is a great opportunity for prospective PhD students interested in doing cutting-edge research 🧪 on ubiquitin!
🚨New preprint! We built a cell-free genomics platform (GATO-seq) to probe transcriptional regulation and discovered a “super pause” sequence that triggers a new Pol II active-site conformation. Huge shout-out to @robertovn.bsky.social for pulling off this monster of a project. tinyurl.com/superpause
🚨Preprint alert🚨 How does chromatin “architecture” form at CTCF sites? Our new preprint with @voslab.org and @andersshansen.bsky.social shows CTCF dimerization promotes nucleosome oligomerization on chromatin. tinyurl.com/CTCF-nucleos...
Happy to share part of my postdoctoral work at the @lucas.farnunglab.com lab. Great collaboration with @voslab.org and @andersshansen.bsky.social. “Structural basis for CTCF-mediated chromatin organization” www.biorxiv.org/content/10.6...
🧪🧬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...
Formation & function of #MembranelessOrganelles! #CryoET structures of #proteasome storage granules inside cells!
Read our paper @cp-cell.bsky.social!
❕Publication: doi.org/10.1016/j.ce...
❕Press Release: www.biochem.mpg.de/en/pressroom
@uoftmedicine.bsky.social
@erc.europa.eu #UPSmeetMet
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)
Pour a glass of champagne AND red Bordeaux—Our newest work with GSK @scripps.edu is out in @nature.com! Here we describe SB-405483, the first allosteric CRBN ligand which potentiates neosubstrate degradation. Congrats Vanessa and all authors! 🍷💫💐 www.nature.com/articles/s41...
This is also a good occasion to highlight that we are looking for post-doctoral researchers that are interested in understanding the fundamental mechanisms of transcription, DNA replication, and chromatin.
Check out the newest preprint from the Schulman lab 🎊🎉
Super cool mechanism of how a metabolite regulates the stability of its own metabolizing enzyme!
Alina did it all for this project CRISPR screen ✂️, biochemistry 🧪, and cryo-EM ❄️🔬.
Congrats!
What happens when E3 Ubiquitin Ligase and RNA Enthusiasts team up!
Massive congrats to this transatlantic collaboration between @jakobfarnung.bsky.social from Schulman Lab and @elenaslo.bsky.social from @bartellab.bsky.social
Have a read!
