Xiuzhen Chen

KDM6B-dependent epigenetic programming of uterine fibroblasts in early pregnancy regulates parturition timing in mice Parturition timing in mice is controlled by locus-specific adjustment of histone H3 trimethyl lysine 27 (H3K27me3) levels within uterine fibroblasts in early gestation, with subsequent locus-specific ...

www.cell.com/cell/abstrac...

Condensate with a function 👍

Targeting FOXM1 condensates reduces breast tumour growth and metastasis - Nature The transcription factor FOXM1 forms functional condensates, the formation of which can be targeted with a specific peptide to suppress breast cancer growth and metastasis.

Nature research paper: Targeting FOXM1 condensates reduces breast tumour growth and metastasis

https://go.nature.com/4g7BNC8

Paperpile for Word - Paperpile

Y'all, there is now a Paperpile extension for Word. This should be useful for a lot of us who have heavy Word users and heavy Google Doc users on the same writing teams. paperpile.com/word-plugin/

1/ In March 2023, I received a lumbar puncture. This was key to receiving my chronic inflammatory demyelinating polyneuropathy #cidp diagnosis. This 🧵 is on my experience with identifying and treating #autoimmunedisease. I'll also be sharing some 🧵s I posted previously on the Other Place.

Opinion | Pfizer Stopped Us From Getting Ozempic Decades Ago (Gift Article) Researchers identified one key breakthrough for GLP-1 drugs in the 1980s, but Pfizer walked away.

An interesting read on the alternative history of GLP1 www.nytimes.com/2024/12/25/o...

Cellular RNAs directly regulate the activity of an antiviral immune signaling complex
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
@science.org @nandangokhale.bsky.social @ramlabuw.bsky.social

The life of each of us began when a sperm and an egg came together. But what happens at a molecular level?

Our latest work in Cell led by @vdeneke.bsky.social & Andreas Blaha reveals a conserved fertilization complex that bridges sperm and egg in vertebrates! (1/11)

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

RNA looping!

Going nuclear: Improved antisense oligonucleotide activity through conjugation with a nuclear importer Antisense oligonucleotides (ASOs) are a promising class of therapeutics designed to modulate gene expression. Both key mechanisms of action for ASOs operate in the nucleus: splice-switching ASOs modif...

We have dramatically increased the activity of splice switching *and* RNase H-active antisense oligonucleotide #ASO therapeutics by conjugating a nuclear importer 🧬💊!

Preprint led by Disha
#chemsky 🧪 @uclchemistry.bsky.social @oxfordchemistry.bsky.social chemrxiv.org/engage/chemr...

We designed MS2 and PP7 binding coat proteins that are degraded in cells except when bound by their hairpin RNAs.

You can check out our pre-print here: tinyurl.com/27p7hyt9,
and listen to a Google AI-generated podcast on it here: notebooklm.google.com/notebook/d71...

Stereochemistry in the disorder–order continuum of protein interactions - Nature Studies on protein–protein interactions using proteins containing d- or l-amino acids show that stereoselectivity of binding varies with the degree of disorder within the complex.

We did this crazy project where we tried to see if proteins could interact with their mirror image ligand. Seems impossible when proteins need to form 3D structures to interact. But what about if the interaction remains disordered???

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

snoRNA-facilitated protein secretion revealed by transcriptome-wide snoRNA target identification Transcriptome-wide mapping of snoRNA targets reveals mRNA-snoRNA-7SL RNA ternary interactions, which facilitate nascent protein translocation to the ER and subsequent secretion.

www.cell.com/cell/fulltex...
#snoRNA #RNAsky #RNA

Nifty, innovative approach

Came to a new understanding of 'colocalization' since starting STED microcopy: there is no colocalizaiton, objects cannot occupy the same physical space!

Graphical abstract of the paper.

How long does an mRNA stay in the nucleus? How long does it stay in the cytoplasm? In an amazing collaboration with @landthalerm.bsky.social, we used metabolic labeling, cell fractionation and mathematical modeling to quantify mRNA flow through the cell. Finally out in MSB: doi.org/10.1038/s443...

Specific tRNAs promote mRNA decay by recruiting the CCR4-NOT complex to translating ribosomes The CCR4-NOT complex is a major regulator of eukaryotic messenger RNA (mRNA) stability. Slow decoding during translation promotes association of CCR4-NOT with ribosomes, accelerating mRNA degradation....

I’m thrilled to share a collaborative story from @Mendell_lab and Jan Erzberger labs, led by postdoc extraordinaire Xiaoqiang Zhu. We showed that in addition to their canonical decoding function, tRNAs play a key role in regulating mRNA stability during translation!
www.science.org/doi/10.1126/...

Failing to account for RNA quantity inflates background and leads to the misleading appearance that PRC2 and GFP bind to RNA in vivo We recently published biochemical and quantitative evidence that challenges the widespread claims that PRC2 binds directly to many RNAs in vivo . A recent preprint performs a re-analysis of some of ou...

A report made counterintuitive claims that PRC2 binds
→ more RNA than PTBP1 & hnRNPU
→ RNAs that do not exist in the cell

We found a simple explanation: the authors ignore most RNA in the sample, leading to inflated background & misleading conclusions.

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

Red-bellied Woodpecker clinging to the side of a huge Tulip tree

Missed the woodpecker sweep by 1 at Green-Wood Cemetery this morning. Tallied Yellow-bellied Sapsucker, Red-headed Woodpecker, Red-bellied Woodpecker, Downy Woodpecker & Northern Flicker. Oddly, Hairy Woodpecker is rare here despite breeding at nearby Prospect Park #birds #birdsNYC

Schematic overview of the proposed mode of action of the newly discovered REX element. Top: An enhancer can activate a gene at a short distance, but not at at long range. Middle: Presence of (C/T)AATTA motifs within an enhancer enable it to act over long distances. Bottom: Coupling a short-range enhancer to the REX element containing the same motifs turns it into a long-range enhancer.

REX - a mammalian "range extender" element that can turn short-distance enhancers into long-distance enhancers.

New preprint from a collaboration led by Grace Bower and Evgeny Kvon.

doi.org/10.1101/2024...

I've been meaning to write a lengthy thread about our experiences with DNA methylation editing in mouse ESCs if that would be useful (or interesting?) for a niche audience here. tl;dr: it was frustrating but we learned a lot, and it ended with our shiny new pub (1/17) www.nature.com/articles/s41...

📌

A beautiful example of mRNA-mRNA interaction demonstrating architectural role for RNP granule formation.

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

A green lifetime biosensor for calcium that remains bright over its full dynamic range Fluorescent biosensors toggle between two states and for the vast majority of biosensors one state is bright and the other state is dim. As a consequence, there is a substantial difference in the sign...

Happy to announce our new preprint "A green lifetime biosensor for calcium that remains bright over its full dynamic range" which is now available on bioRxiv:
www.biorxiv.org/content/10.1...

Why yet another biosensor for Ca2+? Here's a thread 🧵