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Posts by Michaela Müller-McNicoll

Video

I am so excited to share our new findings with you! We provide the structural evidence for a direct protein-to-DNA information pathway, showing how a bacterial enzyme 'reads' its own structure to 'write' DNA. www.science.org/doi/10.1126/...

5 days ago 217 98 6 11
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Multivalent 28S rRNA expansion segments enable reconstitution of multilayered nucleolar architecture Wei et al. demonstrate that 28S rRNA expansion segments are critical for multilayered nucleolar architecture formation through multivalent RNA-RNA interactions. Expansion segments from tripartite-nucleolus species confer enhanced multivalency of 28S rRNA, and transferring these segments across species is sufficient to induce nucleolar-like layered structures in vitro.

Multivalent 28S rRNA expansion segments enable reconstitution of multilayered nucleolar architecture

4 days ago 2 1 0 1

there goes the central dogma, i guess. is nothing sacred anymore?

4 days ago 51 9 3 0

NAR breakthrough alert 🎉 Joint work with @mfeldbruegge.bsky.social on Rrm4. We dissect its modular RRM binding code & how domain combinations shape RNA interactions. Like finding needles in a haystack, comparative iCLIP sorts functional vs accessory sites. Work by Nina & @srimeenakshi.bsky.social

2 weeks ago 14 3 0 2
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Facts spoken by an ex-trumper...

2 weeks ago 27477 8851 67 776
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Mechanosensory channels mediate ER Ca2+ transients to trigger assembly of autophagosome initiation sites for degradation of ER subdomains Ma et al. show that stress-induced, high-luminal Ca2+ ER sheets are selectively degraded by autophagy (ER-phagy), which requires the concerted actions of FAM134B and lipidated LC3. The ER-localized channels PIEZO1 and TRPV1 mediate Ca2+ release from these ER subdomains, triggering the formation of FIP200 puncta to initiate autophagosome assembly.

Mechanosensory channels mediate ER Ca2+ transients to trigger assembly of autophagosome initiation sites for degradation of ER subdomains

2 weeks ago 8 4 0 0
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Our paper is now out in Science! Super excited to share our discovery that #mitochondria #pearling is the elusive mechanism driving the regular distribution and inheritance of #mtDNA nucleoids 🧬 [1/6]

2 weeks ago 173 64 3 5
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Nuclear speckles of GC richness - Nature Reviews Molecular Cell Biology Nuclear speckles support the splicing of levelled exon–intron architecture transcripts, and their evolution shaped genome organization in amniotes.

The research highlight of our recent work on nuclear speckles is online. The photo choice is eggcellent. Happy Easter! 🌸🐰🥚
www.nature.com/articles/s41...

2 weeks ago 42 14 0 0
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Quantifying Protein Homodimer Affinities and the Effect of Molecular Glues and Interface Residues Using Native Mass Spectrometry Biological processes rely on finely tuned homo- and heteromeric interactions between (biomacro)molecules. The strength of an interaction, typically given by the dissociation constant (KD), plays a crucial role in basic research and must be monitored throughout the development of drugs and agrochemicals. An ideal method for KD determination is applicable to various analytes with a large range of affinities, tolerates complex matrix compositions, does not require labeling, and simultaneously provides information on the structural integrity of the binding partners. Native mass spectrometry meets these criteria but typically struggles with homooligomeric complexes due to overlapping mass signals. To overcome this, we resolve monomer/dimer contributions to overlapping MS-peaks by separately analyzing the charge state distribution of each oligomeric species via sample dilution and covalent cross-linking. Following this approach, we show that quantitative laser-induced liquid bead ion desorption mass spectrometry (qLILBID-MS) accurately captures the affinities of Bovine Serum Albumin (BSA) and chemically induced dimers of Tryparedoxin (Tpx), an oxidoreductase from human pathogenic Trypanosoma brucei parasites, with various molecular glues and homodimer affinities. Conveniently, qLILBID-MS requires a fraction of sample used by other methods such as isothermal titration calorimetry (ITC) and yields previously inaccessible protein homodimer KDs in the high micromolar range, which allowed us to monitor the gradual decrease in homodimer affinity via mutation of crucial dimer interface contacts. Overall, qLILBID-MS is a sensitive, robust, fast, scalable, and cost-effective alternative to quantify protein/protein interactions, that can accelerate contemporary drug discovery workflows, e.g. the efficient screening for proximity inducing molecules like proteolysis targeting chimera (PROTACs) and molecular glues.

New paper out with our friends the Nina Morgner Lab on how to quantify homodimer affinities by native MS 💕
pubs.acs.org/doi/10.1021/...

Never thought it possible, but this concludes our JACS triple - 3 papers in 3 months 😋🥳🧪

@crc1507.bsky.social @microverse.bsky.social
@lifeprofile.bsky.social

2 weeks ago 20 5 0 1
CryoET and colored segmentation of TMEM106B fibrils protruding from within a broken lysosome in post-mortem FTLD-GRN brain.

CryoET and colored segmentation of TMEM106B fibrils protruding from within a broken lysosome in post-mortem FTLD-GRN brain.

Excited to share a pre-print from a collaboration between my lab at NIH, Len Petrucelli's lab at University of Miami, and Shyamal Mosalaganti's lab at University of Michigan.

3 weeks ago 33 9 4 0

well done Juliet.

1 month ago 3 1 0 0
Video

A new mechanism for “RNA memory”! This time in Planaria! (Here's a video of a Planarian with mulitple heads, one of the heritable phenotypes we studied).

This work summarizes >10 years of research and is an amazing collaboration with the labs of Jochen Rink and Omri Wurtzel labs. Read thrad below👇

1 month ago 180 45 3 5
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'Virtual cell' captures most-basic process of life: bacterial division Nature - Researchers simulated nearly every molecule in a bacterial cell — and then watched the cell grow and reproduce.

For the first time, researchers have simulated nearly every chemical reaction in a living bacterial cell

go.nature.com/4bp0jOy

1 month ago 80 22 0 5

This is exactly why I left Spain, my family and friend, 13 years ago

1 month ago 50 11 3 0
Image from their link showing evidence of fabricated references

Image from their link showing evidence of fabricated references

Holy smoke. What ultimately happened???

1 month ago 213 77 9 21
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Regulatory paradigm of Dscam1 stochastic alternative splicing through conserved long-range RNA structures Abstract. Pancrustacean Dscam1 genes encode 2 000–120 000 distinct isoforms via mutually exclusive splicing; however, the underlying regulatory mechanisms

academic.oup.com/nar/article/...

Check this

1 month ago 9 3 0 0
Career effects of preprints get mixed reviews from biomedical researchers Junior researchers are more likely to embrace preprints; grant reviewers and hiring committees express doubts

“Hiring, promotion, and funding decisions often still revolve around traditional journal publications.”

www.science.org/content/arti...

1 month ago 5 2 1 0

Happy to share our new preprint on the mechanism of human tRNA 3' CCA maturation! This project was spearheaded by Bernhard Kuhle in my group, with contributions from many others and a great collaboration with the group of Peter Rehling (UMG). See highlights below!

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

1 month ago 25 14 1 0

That’s a very good question Oded and I think it’s exactly what I would need. But somehow I cannot make up my mind, everything seems possible right now but is also changing so fast 😅. What about you?

1 month ago 1 0 1 0

The iCLIP3 protocol was developed by Vlado Despic in a close and fun collaboration with @koenig-lab.bsky.social and @zarnack-group.bsky.social. The protocol was inspired by and successfully tested in the @embo.org #iCLIPcourse thanks to Elias Bechara, Chris Sibley and @rosario-avolio.bsky.social

1 month ago 10 4 0 0
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Control of retrotransposon-driven activation of the interferon response by the double-stranded RNA binding protein DGCR8 Abstract. The type I interferon (IFN) response is the main innate immune pathway against viruses in mammals. This pathway must be tightly regulated to prev

I'm so happy to share our latest paper! Now out in @narjournal.bsky.social 🥳

Did you know that transposable elements embedded in mRNAs can form dsRNA and activate innate immunity? 🧬🦠 Have a look! academic.oup.com/nar/article/...

#TEsky #RNAsky #RNAbiology #immunity #NAR

1 month ago 45 18 2 4

Want to map protein-RNA interactions? Check out our new iCLIP3 protocol. Featuring steamlined library prep and visualisation of protein-RNA complexes without radioactivity! Bioinformatics workflow on top :)

With the Müller-McNicoll and Zarnack labs!
@zarnack-group.bsky.social @mixmue.bsky.social

1 month ago 18 7 0 0
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Exciting news:
Our RNA community in @uniregensburg.bsky.social is set to grow!

We are opening a Junior Group Leader position in RNA biochemistry / ribonucleases / RNA stability. A great opportunity to start your own team within our collaborative RNA network.

Details & application 👇

1 month ago 17 22 1 1

Key upgrades:
• Infrared 3′ RNA labeling with pCp-IR750 for visualization of RBP–RNA complexes — no radioactivity
• Silica column–based RNA recovery — no organic solvents
• Updated adapters for Tru-seq library multiplexing
• Detailed bioinformatics pipelines to identify crosslink events

1 month ago 4 0 0 0

We are excited to share our new preprint: iCLIP3 — an improved protocol for transcriptome-wide mapping of protein–RNA interactions at single-nucleotide resolution.

1 month ago 32 15 1 2
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It’s finally out! Together with @embopress.org and
@reviewcommons.org, we conducted a structured side-by-side comparison of human peer review and our AI scientific review (see thread 👇👇👇🔥).

1 month ago 78 38 2 4
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Giant DNA viruses encode a hallmark translation initiation complex of eukaryotic life Giant DNA viruses encode a cap-binding complex homologous to eIF4F, the defining translation-initiation complex of eukaryotes. The viral cap-binding complex is required for viral protein synthesis and...

www.cell.com/cell/fulltex...

1 month ago 9 3 0 0
An intrinsically disordered region mediates RNA-binding selectivity and cellular activities of LARP6 - Nature Communications LARP6 is an EMT-associated RNA-binding protein with diverse RNA targets. Here, the authors show that the N-terminal disordered region of LARP6 promotes RNA-binding selectivity by modulating the adjace...

🎉Proud to present our latest paper, out now in Nature Communications: www.nature.com/articles/s41...

RNA Binding Proteins (RBPs) are often full of intrinsically disordered regions (IDRs), but what these regions do during RNA recognition is often unclear. 1/10
#RNA #IDR #RBP

2 months ago 75 34 1 4
A multivalent adaptor mechanism drives the nuclear import of proteasomes - Nature Communications Nuclear protein homeostasis relies on proteasome import into the nucleus. Here the authors identify how assembled human proteasomes are transported across the nuclear pore complex and reveal a mechani...

This is a video summarizing our recent paper (www.nature.com/articles/s41...)

youtu.be/eNY2CRlYTRo

2 months ago 25 11 1 0

Updated architectural model of the NPC from our lab, starred by bsky-less Agnieszka Obarska-Kosińska. Using cryo ET, XL-MS and modeling, we identify novel nucleoporins, among those the mRNA export complex TREX-2! Check out the preprint on biorxiv #TeamMassSpec #TeamTomo

1 month ago 10 2 0 0