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Stirling Churchman @stirlingchurchman.bsky.social · Sep 9

An exciting study driven by the close collaboration of first authors @erinduffyphd.bsky.social and @inespatop.bsky.social. And thanks to our other colleagues for making this such a comprehensive study. (11/11)

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Stirling Churchman @stirlingchurchman.bsky.social · Sep 9

This work reveals RNA stability as a "hidden layer" of gene regulation that: 1) Operates independently of transcription 2) Works locally in neuronal processes 3) Is disrupted in neurodevelopmental disorders 4) Expands our view of activity-dependent plasticity (10/11)

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Stirling Churchman @stirlingchurchman.bsky.social · Sep 9

Importantly, HuD-bound mRNAs are enriched for autism spectrum disorder (ASD) risk genes, and ASD variants can alter RNA stability regulation, implicating this pathway in neurodevelopmental disorders. (9/11)

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Stirling Churchman @stirlingchurchman.bsky.social · Sep 9

How does activity change HuD function? Not by changing HuD levels, but by reorganizing its protein partners. Microscopy and IP-MS support a model where activity recruits HuD into RNA granules, stabilizing HuD-bound mRNAs by protecting them from degradation. (8/11)

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Stirling Churchman @stirlingchurchman.bsky.social · Sep 9

We found that activity-dependent gene expression is modulated in both soma and distal processes (dendrites and axons), suggesting neurons may coordinate RNA stability, transport, and translation to adjust protein levels locally. (7/11)

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Stirling Churchman @stirlingchurchman.bsky.social · Sep 9

To gain some mechanistic insight, we used MPRAs, machine learning, RIP-seq and metabolic labeling and identified the RNA binding protein HuD as a key regulator of activity-dependent RNA stability. (6/11)

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Stirling Churchman @stirlingchurchman.bsky.social · Sep 9

And we did some in vivo validation: We also see effects on RNA stability in vivo in response to novel environment exploration, meaning this isn’t just a phenomenon in primary neurons, it also occurs in a physiologically relevant learning paradigm in the intact brain. (5/11)

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Stirling Churchman @stirlingchurchman.bsky.social · Sep 9

RNA stability changes weren’t just a side effect. For ~10% of activity-dependent transcripts, stability mattered more than transcription for determining RNA levels, challenging the transcription-centric view of gene regulation in this process. (4/11)

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Stirling Churchman @stirlingchurchman.bsky.social · Sep 9

Of ~5,000 activity-regulated transcripts, two thirds showed changes in transcription, which was expected. Unexpectedly, ~1,000 genes were regulated by RNA stability.(3/11)

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Stirling Churchman @stirlingchurchman.bsky.social · Sep 9

When neurons fire, they need to rapidly change which genes are expressed to support processes like long-term memory. Transcriptional responses are well studied, but what about other steps in the RNA life cycle? (2/11)

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Stirling Churchman @stirlingchurchman.bsky.social · Sep 9

Our new pre-print from the Greenberg and Churchman labs shows that activity-dependent modulation of RNA stability is a major, and underappreciated, mechanism of gene regulation in neurons. Tutorial below! www.biorxiv.org/content/10.1... (1/11)

HuD controls widespread RNA stability to drive neuronal activity-dependent responses

Neuronal activity shapes brain development and refines synaptic connectivity in part through dynamic changes in gene expression. While activity-regulated transcriptional programs have been extensively...

www.biorxiv.org

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Stirling Churchman @stirlingchurchman.bsky.social · Aug 19

I was inspired and made one last night! So good.

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Stirling Churchman @stirlingchurchman.bsky.social · Aug 18

I'm late to this! That's the real deal! Go make a 1919 ASAP. :)

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Reposted by Stirling Churchman

Michela Palamin @mpalamin.bsky.social · Jul 21

First time posting here — and first-ever Single Molecule Conference 🧬

Held right at @embl.org Heidelberg, where I work!

4 days full of great science and great people. Fantastic meeting! 🔬

Curious to see where the single molecule field is going next! 👀

#EMBLSingleMolecule @events.embl.org

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Reposted by Stirling Churchman

Masa A. Shimazoe @masaashimazoe.bsky.social · Jul 18

Honored to receive 1st Place Poster Award 🏆 at the EMBL meeting "Gene Regulation: One Molecule at a Time"!
Thank you to all who visited and engaged in exciting discussions.
Grateful to the organizers for an excellent event! #EMBLSingleMolecule

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Reposted by Stirling Churchman

Arnaud Krebs @arnaudkr.bsky.social · Jul 18

#EMBLsinglemolecule was a blast! Happy to host the birth of single molecule genomics as a field and to think about the future with the microscopy crowd. Thanks to participants and organizers!

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Stirling Churchman @stirlingchurchman.bsky.social · Jul 18

The molecular feedback mechanisms that maintain yeast mito-nuclear balance represent elegant solutions to a major vulnerability in eukaryotic cells. I was privileged to be involved in this fascinating study!

Martin Ott lab @mitolab.bsky.social · Jul 18

In a new study by our @pelleeas.bsky.social, we reveal how Mrx4 organizes translational regulation of cytochrome b synthesis at the mitoribosomal tunnel exit. Thanks @kawresearch.bsky.social for funding and @stirlingchurchman.bsky.social for the fun collaboration! academic.oup.com/nar/article/...

A molecular switch at the yeast mitoribosomal tunnel exit controls cytochrome b synthesis

Abstract. Mitochondrial gene expression needs to be balanced with cytosolic translation to produce oxidative phosphorylation complexes. In yeast, translati

academic.oup.com

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Reposted by Stirling Churchman

Martin Ott lab @mitolab.bsky.social · Jul 18

In a new study by our @pelleeas.bsky.social, we reveal how Mrx4 organizes translational regulation of cytochrome b synthesis at the mitoribosomal tunnel exit. Thanks @kawresearch.bsky.social for funding and @stirlingchurchman.bsky.social for the fun collaboration! academic.oup.com/nar/article/...

A molecular switch at the yeast mitoribosomal tunnel exit controls cytochrome b synthesis

Abstract. Mitochondrial gene expression needs to be balanced with cytosolic translation to produce oxidative phosphorylation complexes. In yeast, translati

academic.oup.com

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Reposted by Stirling Churchman

EMBL Events @events.embl.org · Jul 17

🗨️💡Great conversations during well-attended lunch time panel discussions at #EMBLSingleMolecule

Panel 1️⃣: Single molecule genomics data analysis
Chair: @stirlingchurchman.bsky.social

Panel 2️⃣: Single molecule microscopy data analysis
Chairs: @laghalab.bsky.social, Dan Larson

@arnaudkr.bsky.social

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Reposted by Stirling Churchman

Arnaud Krebs @arnaudkr.bsky.social · Jul 17

Absolutely thrilled of hosting the #EMBLSingleMolecule community together @embl.org for the first time under one roof! Exciting data and prospects!

EMBL Events @events.embl.org · Jul 16

💬❓ We like a good Q&A session – a lot of great questions following every talk at 'Genre regulation: one molecule at a time'! Keep asking yours, both in the auditorium and online 🙌🏼 #EMBLSingleMolecule

@arnaudkr.bsky.social @embl.org

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Reposted by Stirling Churchman

EMBL Events @events.embl.org · Jul 15

🍪 Taking a breather at 'Gene regulation: one molecule at a time' — where the science is complex, but the coffee is simple (and much needed!).
From single-molecule insights to lively hallway conversations, it's clear: breakthroughs happen both in the lab and over lattes. ☕🧬
#EMBLSingleMolecule

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Reposted by Stirling Churchman

Eric Topol @erictopol.bsky.social · Jul 17

A big day for preventing mitochondrial diseases from transmitting to the next generation
www.nature.com/articles/d41...
www.nejm.org/doi/full/10....
www.nejm.org/doi/full/10....
www.nejm.org/doi/full/10....

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Reposted by Stirling Churchman

EMBL Events @events.embl.org · Jul 15

Welcome to the inaugural edition of 'Gene regulation: one molecule at a time' 🤩🧬 #EMBLSingleMolecule
Most of the participants are already on site – now time for some science!
Our Scientific Organisers:
🔹 @stirlingchurchman.bsky.social
🔹@arnaudkr.bsky.social
🔹 @laghalab.bsky.social
🔹 Daniel Larson

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Reposted by Stirling Churchman

Emily Madden @emadden.bsky.social · Jun 18

🧬 🧪The world’s on 🔥 BUT in the interest of sharing small wins, I am helping build something cool at EpiCypher that I'm proud of:

Fiber-seq is an LRS assay that maps chromatin accessibility, DNAme, and DNA sequence on single molecules.

If your jam is functional genomics/epigenetics, check this out.

EpiCypher @epicypher.bsky.social · Jun 18

🚀 We’re launching Fiber-seq, a multiomic approach that combines chromatin accessibility, CpG methylation, and DNA sequence in one long-read sequencing assay.

We’re inviting a limited group of early users to try Fiber-seq at no cost.

Interested? Learn more 👉 explore.epicypher.com/fiber-seq-su...

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Reposted by Stirling Churchman

Life Science Alliance @lsajournal.org · Jun 17

Mitochondrial RNAs can be found in mitochondrial RNA granules (MRGs) where they are processed. However, here the authors show that during transcription arrest, mt-mRNAs form granules distinct from MRGs.
@stirlingchurchman.bsky.social‬
www.life-science-alliance.org/content/8/9/...

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