Sendoel Lab

Third defense this summer officially in the books. Huge congrats to Fabiola for a brilliant presentation and defense! #Summerofdefenses

….and more #gastruloid preprint with proof of how to use their robustness and scalabiliy in high throughput screens to learn about #posttranscriptional regulation of gene expression @ Sendoel and Lutolf labs www.biorxiv.org/content/10.1...

Preprint by the @sendoellab.bsky.social in collab w/ the Lutolf & Zavolan labs w/1st author David Taborsky "Regulation of mRNA polyadenylation governs mammalian body plan formation in gastruloids" @biorxivpreprint.bsky.social
buff.ly/mL3a71T
@dadita.bsky.socia
@mihaelazavolan.bsky.social

How can we identify novel regulators of germ layer differentiation and body patterning? I am happy to announce that my preprint using single-cell CRISPR screens in gastruloids to answer this question is now online! Thank you to the rest of the @sendoellab.bsky.social and all coauthors!

PhDone 🥳🎓

The last few years was full of successes, failures, ups and downs, but also full of amazing people, countless talks, great conferences, incredible science and endless support from my supervisor and my thesis committee. Thanks to all people who helped me in this amazing journey! #eIF2A

The summer of defenses continues, huge congratulations Dr. Yigit for a superbly delivered talk and an excellent defense!

Cross-tissue multicellular coordination and its rewiring in cancer - Nature Comprehensive single-cell transcriptomic analysis of 35 human tissues reveals 12 cross-tissue coordinated cellular modules that exhibit intramodule communication and dynamic changes with ageing, and w...

new out in Nature today www.nature.com/articles/s41...

The very first PhD graduate of our lab! Great science, fantastic presentation and expertly defended. Huge congratulations on this well-earned milestone Dr. Duré!

Preprint by the Sendoel Lab ( @sendoellab.bsky.social ) with first author Merve Yigit ( @merveyigit.bsky.social‬ "The alternative initiation factor eIF2A regulates 40S subunit turnover in ribosome-associated quality control"
@biorxivpreprint.bsky.social‬
buff.ly/hP9Iani
‪@anupamd.bsky.social‬

Collectively, our study identifies a new link between eIF2A and ribosome-associated quality control (RQC), implies that eIF2A promotes translation fidelity by tuning 40S ribosome rescue under stress and warrants further investigations into the role of RQC in tumorigenesis. 6/x

Finally, in lung SCC patient data, we find increased K214-RPS3 ubiquitination, the very site targeted during RQC. RNF10 and eIF2A mRNA levels both correlate with shorter overall survival, pointing to a potential link between RQC induction and tumor progression. 5/x

G3BP1–USP10 complexes rescue stalled 40S from degradation. Using dynamic SILAC in mouse and human cells, we find eIF2A KO cells have reduced 40S turnover under stress, indicating that eIF2A tunes USP10-mediated 40S rescue under stress. 4/x

Consistent with recent ribosome profiling, our 40S TCP-seq analyses reveal only a minimal role in initiation. Rather, eIF2A loss causes a marked reduction in RPS3 ubiquitination upon stalling. We demonstrate that eIF2A antagonizes USP10-mediated deubiquitination of stalled 40S subunits. 3/x

Led by the skilled @merveyigit.bsky.social, we performed TurboID-based proximity biotinylation in both homeostatic and stressed cells. Zooming into 40S interactions, we locate eIF2A near the mRNA entry channel and uncover strong interactions with G3BP1-USP10 complexes as well as RPS2 and RPS3. 2/x

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 pre...

Identified in the 1970s, the precise molecular function of the alternative initiation factor eIF2A has remained unclear. Here, we map its interactome and uncover a surprising role in ribosome-associated quality control (RQC) upon ribosome stalling. 1/x

www.biorxiv.org/content/10.1...

The former GRC Stem Cells & Cancer has found its new home in beautiful Malta, fantastic meeting ahead!

New Night Science Podcast episode! David Baker was awarded the 2024 Nobel Prize in Chemistry. He explains how he socially engineers his lab’s "communal brain", where all individuals function like neurons, densely interconnected to maximize idea generation.
nightscience.buzzsprout.com/1744020/epis...

Preprint by the Sendoel lab ( @sendoellab.bsky.social ) with first author Fabiola Valdivia-Francia ( @fabiolavaldiviaf.bsky.social ) "In vivo single-cell CRISPR screening for microproteins identifies a critical ribosomal component" @biorxivpreprint.bsky.social
buff.ly/Ch7I3Gj

In vivo single-cell CRISPR screening for microproteins identifies a critical ribosomal component The dark proteome includes a rapidly expanding catalog of microproteins with unknown functions that have been historically ignored in genome annotations. Here, we exploit an in vivo single-cell CRISPR...

There is a new must-read paper for the weekend. 👀

Looking for the next future vision of #microprotein research? Check out this from @fabiolavaldiviaf.bsky.social @sendoellab.bsky.social.

Really, what can't microproteins do?

#RNAsky
#genomics
#bioinformatics
🧬 💻

www.biorxiv.org/content/10.1...

Our study establishes a framework for dissecting the functional significance of the dark proteome, uncovers a second Rpl41 gene critical for ribosome function and suggests pseudogenes as potential reservoirs of functional microproteins that expand the cellular proteome. 9/9

Our findings suggest that Gm10076 acts as a second Rpl41 source, explaining mild effects of Rpl41 loss. Knocking down Rpl41 in Gm10076 mutants almost fully halted proliferation. Thus, although RPL41 has been considered non-essential, this intersubunit bridge protein is in fact critical. 8/9

We observed a 40% reduction in overall protein synthesis in Gm10076 mutant keratinocytes. Ribosome profiling and RNA-seq revealed broad changes in the translational landscape, indicating that Gm10076 may contribute significantly to total cellular RPL41 levels. 7/9

We identified Gm10076 perturbation as the top depleted hit. This 25-amino-acid microprotein, encoded on the Gm10076 lncRNA, fully matches the RPL41 protein sequence, suggesting the existence of a second Rpl41 gene and prompting us to explore its role at the intersubunit bridge of the ribosome.6/9

We then validated 29 microproteins in a secondary screen both in vivo and in vitro, resulting in a high-confidence list of candidate microproteins that consistently displayed the same phenotype. 5/9

Notably, a cohort of 14 microprotein perturbations induced substantial transcriptional changes across the major epidermal cell types, suggesting that this subset of microproteins globally shapes gene expression and cellular function. 4/9

By combining scRNA-seq with sgRNA capture, we investigated 229 of these microproteins and systematically mapped cell-type-specific microprotein function at single-cell transc. resolution. We discovered global and cell-type specific gene expression alterations upon microprotein perturbations. 3/9

Spearheaded by the very talented @fabiolavaldiviaf.bsky.social and another great collaboration with the Ellis lab, we used ribosome profiling to map microproteins in healthy epidermis and cancer, annotating more than 3000 novel ORFs. 2/9

Our genome encodes > 7000 microproteins that have been previously ignored in genome annotations. How do these microproteins impact tissue function? Here, we use an in vivo single-cell CRISPR screen to systematically explore microprotein function in the mouse epidermis. 1/9

A small appeal to young scientists looking for internship and PhD positions - websites are hard to maintain, papers can take years to publish & often end up behind a paywall. Read the preprints if you really want to know what a lab is up to.

If they don’t preprint… this tells you something too ;)

📅 Program of the NCCR RNA & Disease Seminar Series for the Spring Semester 24/25:

News entry NCCR website, incl. titles: lnkd.in/dMZAmeHg

@unibern.bsky.social @ethzurich.bsky.social @snsf-ch.bsky.social