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David McQuarrie

@davidmcquarrie

Postdoc in the Jaffrey lab at @WeillCornell.bsky.social @CornellUniversity.bsky.social former PhD in the Soller lab interested in RNA-binding proteins and RNA modifications; #RNA #RNAmodifications #Genetics 🧫πŸͺ° #MolecularBiology #Evolution

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10.11.2024
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Latest posts by David McQuarrie @davidmcquarrie

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m6A is the most common internal mRNA modification, but we still don't know what most m6A sites actually DO.

Zhang et al. built FOCAS -- a CRISPR-based platform using dCas13b-FTO to precisely remove m6A at specific sites without touching the DNA.

doi.org/10.1016/j.c...

26.02.2026 15:15 πŸ‘ 6 πŸ” 2 πŸ’¬ 1 πŸ“Œ 0
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A retroelement-derived mammalian ARC protein exhibits selective RNA recognition and nucleic acid chaperone functions - PubMed Activity-regulated cytoskeleton-associated protein (ARC) is an RNA-binding protein that also serves as a central hub for neuronal protein-protein interactions. It is essential for intercellular signaling and contributes to synaptic plasticity. ARC includes Gag-like sequences of Ty3/Gypsy retrotransp …

#TEsky A retroelement-derived mammalian ARC protein exhibits selective RNA recognition and nucleic acid chaperone functions pubmed.ncbi.nlm.nih.gov/41797537/

09.03.2026 19:30 πŸ‘ 9 πŸ” 6 πŸ’¬ 0 πŸ“Œ 0
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DICER cleavage fidelity is governed by 5β€²-end binding pockets - Nature Cryo-electron microscopy and massively parallel assays shed light on the mechanism by which DICER, a key enzyme in the RNase III family, cleaves RNA at precise locations to produce small RNAs.

this seems to be a very interesting paper on the (reality) and the significance of 5'G micorRNAs for Dicer processing

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

07.03.2026 17:38 πŸ‘ 6 πŸ” 2 πŸ’¬ 0 πŸ“Œ 0
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RNA-specific local translation is patterned by condensates for multinucleate cell growth - Nature Cell Biology Geisterfer, Jalihal et al. show spatially distinct effects of Whi3 condensates on target translation in Ashbya syncytia. In vitro, translation is enriched at condensate–solute interfaces but repressed...

Condensates are powerful ways to break symmetry and cells do remarkable things with them. Here we show that in a multinucleate fungus, a condensate regulates translation of a cyclin and a formin in distinct locations.
www.nature.com/articles/s41...

08.03.2026 18:05 πŸ‘ 106 πŸ” 38 πŸ’¬ 1 πŸ“Œ 0
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I'm sorry, 50 what now?

"We present a GPU implementation of kallisto for RNA-seq transcript quantification (...). For a large dataset of 295 million reads, runtime drops from 40 minutes to 50 seconds"

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

07.03.2026 01:12 πŸ‘ 41 πŸ” 12 πŸ’¬ 2 πŸ“Œ 5
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Spligation enables programmable chimeric RNA generation in living cells
doi.org/10.64898/202...

07.03.2026 12:14 πŸ‘ 8 πŸ” 5 πŸ’¬ 0 πŸ“Œ 0

Evolutionary emergence and preservation of microproteins encoded by upstream ORFs https://www.biorxiv.org/content/10.64898/2026.03.05.709866v1

06.03.2026 15:33 πŸ‘ 5 πŸ” 5 πŸ’¬ 1 πŸ“Œ 0
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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

07.03.2026 09:48 πŸ‘ 9 πŸ” 3 πŸ’¬ 0 πŸ“Œ 0

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

04.03.2026 20:23 πŸ‘ 27 πŸ” 13 πŸ’¬ 1 πŸ“Œ 2

Out now! In collaboration with Leifu Chang, we uncover the molecular and structural underpinnings of CRISPR-Cas12f-like RNA-guided transcription systems!

Links to the published articles:
tinyurl.com/55kpavet
tinyurl.com/sk6djwx3

Previous thread for the preprint:
bsky.app/profile/did:...

04.03.2026 20:28 πŸ‘ 69 πŸ” 26 πŸ’¬ 0 πŸ“Œ 2
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Interstep compatibility of a model for the prebiotic synthesis of RNA consistent with Hadean natural history | PNAS Models for prebiotic syntheses often have many steps, each separately validated by laboratory experiments. The challenge then asks whether these st...

RNA from scratch.. πŸ’« Interstep compatibility of a model for the prebiotic synthesis of RNA consistent with Hadean natural history | PNAS
www.pnas.org/doi/10.1073/...

04.03.2026 07:01 πŸ‘ 5 πŸ” 3 πŸ’¬ 0 πŸ“Œ 0
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After 5 years of developing, a new preprint from the lab - introducing our workflow for comparative insect connectomics, aimed at democratizing connectomics. @erc.europa.eu @lundvision.bsky.social @biologylu.bsky.social Read it here: www.biorxiv.org/content/10.6...

01.03.2026 20:58 πŸ‘ 82 πŸ” 40 πŸ’¬ 2 πŸ“Œ 1

23S rRNA modifications stimulate catalytic activity and prevent the formation of alternative structures https://www.biorxiv.org/content/10.64898/2026.03.01.708810v1

03.03.2026 05:18 πŸ‘ 2 πŸ” 1 πŸ’¬ 0 πŸ“Œ 0
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Gene body methylation buffers noise in gene expression in plants Abstract. Non-genetic variability in gene expression is an inevitable consequence of the stochastic nature of processes driving transcription and translati

Hot off the press, our latest publication on the functional role of gene body methylation (gBM).

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

Work spearheaded by Jakub Zastapilo with help from @robynemm.bsky.social and Liudmila Mikheeva and co-led by Marco Catoni and @ubechtold.bsky.social 1/3

17.02.2026 13:41 πŸ‘ 16 πŸ” 11 πŸ’¬ 2 πŸ“Œ 0
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Hmmmm. β€œMars Potato Cultivation: Analysis, Challenges, Sustainable Scientific Conceptions”

#plantscience #astrobiology

pubmed.ncbi.nlm.nih.gov/41752916/

28.02.2026 13:45 πŸ‘ 6 πŸ” 2 πŸ’¬ 1 πŸ“Œ 0
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Paralog interference contributes to the preservation of genetic redundancy Duplicated self-interacting proteins can interact and interfere with each other’s function. Cisneros, Mattenberger, et al. show that selection against interfering loss-of-function alleles extends the ...

New paper alert: Paralog interference contributes to the preservation of genetic redundancy www.cell.com/current-biol...

28.02.2026 02:00 πŸ‘ 45 πŸ” 28 πŸ’¬ 0 πŸ“Œ 0

We wrote a piece on how easy it is to write gene regulatory sequences. - Turns out, it isn't that easy even though we know a lot about cis-regulation.

huge credit to @carldeboer.bsky.social to seeing this through so our thoughts aren't lost. I promise, it's a worthwhile read!

27.02.2026 08:27 πŸ‘ 28 πŸ” 12 πŸ’¬ 0 πŸ“Œ 0
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Chromatin spatial analysis by METALoci unveils sex-determining 3D regulatory hubs Nature Structural & Molecular Biology - METALoci, a new three-dimensional genome computational tool, reveals a major rewiring of regulatory interactions during sex determination. By combining...

🀩πŸ’ͺ Out now! 3D regulatory hubs in sex determination

With @mamartirenom.bsky.social & Capel labs, led by @imotagom.bsky.social & @jrotwitguez.bsky.social

1️⃣ METALoci – explore #3DGenome 🧬
2️⃣ Non-coding region controlling Fgf9 🧩
3️⃣ Meis genes = new key players 🌟

πŸ‘‰ rdcu.be/e5sm2

1/n Bluetorial πŸ‘‡

24.02.2026 14:02 πŸ‘ 59 πŸ” 26 πŸ’¬ 1 πŸ“Œ 2
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Have you ever wondered πŸ€”... Does phenotypic variance respond to environmental perturbation? Does it have a genetic basis? Are mean and variance regulating loci exposed to different selection pressures? These and more questions are explored in our new preprint πŸ”₯

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

23.02.2026 15:37 πŸ‘ 85 πŸ” 48 πŸ’¬ 2 πŸ“Œ 4

LINE-L1, HIV, Ty3 retrotransposons in insects.
several of these genomes are > 40% adenosine!

What is the molecular origin & evolutionary pressure resulting in A-rich genomes of retrotransposons & some retroviruses?

it must be so hardwired that hosts exploit this bias for genome defense

any ideas?

23.02.2026 18:47 πŸ‘ 12 πŸ” 4 πŸ’¬ 2 πŸ“Œ 0
Two-panel figure linking piRNA production to uridine. Left: distributions of piRNA biogenesis efficiency for CDS and 3β€²UTR tiles grouped into efficiency bins (log scale). Right: violin plots showing uridine content (%) in the analysis window for each efficiency bin; higher-efficiency bins have higher U content, indicating U-rich sequence associates with stronger piRNA output.

Two-panel figure linking piRNA production to uridine. Left: distributions of piRNA biogenesis efficiency for CDS and 3β€²UTR tiles grouped into efficiency bins (log scale). Right: violin plots showing uridine content (%) in the analysis window for each efficiency bin; higher-efficiency bins have higher U content, indicating U-rich sequence associates with stronger piRNA output.

We discovered that Yb acts as a U-content sensor. It selectively channels uridine-rich transcripts to piRNA biogenesis, effectively initiating their phased processing into piRNAs. (6/19)

13.02.2026 15:11 πŸ‘ 7 πŸ” 4 πŸ’¬ 1 πŸ“Œ 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...

πŸŽ‰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

21.02.2026 23:31 πŸ‘ 75 πŸ” 33 πŸ’¬ 1 πŸ“Œ 4
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Pseudouridine selects RNAs for extracellular transport RNAs move through the extracellular space to transmit information between cells, including mammalian neurons, yet how specific RNAs are channeled into these extracellular routes is unknown. Using geno...

RNAs outside of cells?! How did they get there?

(Thread coming soon πŸ‘€)

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

30.10.2025 20:07 πŸ‘ 16 πŸ” 6 πŸ’¬ 0 πŸ“Œ 0
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Single-round evolution of RNA aptamers with GRAPE-LM - Nature Biotechnology Combining generative AI and one round of wet lab evolution generates high-affinity RNA aptamers.

Single-round evolution of RNA aptamers with GRAPE-LM go.nature.com/4bFDI22

06.02.2026 15:47 πŸ‘ 7 πŸ” 3 πŸ’¬ 1 πŸ“Œ 0

Happy to share scHiCAR, an ultra-high throughout (millions of cells), low cost (5 cents/cell including NGS), and trimodal platform for integrated single-cell level analysis of mRNA, open chromatin, and 5-kb resolution looping with ground-truth data the same individual cell.

20.02.2026 02:51 πŸ‘ 78 πŸ” 33 πŸ’¬ 0 πŸ“Œ 6
Top:  A representative modeling example from Chimpanzee CPEB3 HDV-like ribozyme (PDB ID: 7QR3), with models predicted by four better-performing methods (blue cartoons) overlaid on experimental structure (gray cartoons). Left to right: DRFold2, DeepFoldRNA, AlphaFold3, RhoFold. Bottom: Structural visualization of the example from coxsackievirus B3 cloverleaf RNA (PDBID: 8DP3), showing experimental structure (left), AlphaFold3’s best prediction from 100 models (middle), and 5th model of DRfold2 (right), respectively. Structures are rainbow-colored from 5β€² (blue) to 3β€² (red) end.

Top: A representative modeling example from Chimpanzee CPEB3 HDV-like ribozyme (PDB ID: 7QR3), with models predicted by four better-performing methods (blue cartoons) overlaid on experimental structure (gray cartoons). Left to right: DRFold2, DeepFoldRNA, AlphaFold3, RhoFold. Bottom: Structural visualization of the example from coxsackievirus B3 cloverleaf RNA (PDBID: 8DP3), showing experimental structure (left), AlphaFold3’s best prediction from 100 models (middle), and 5th model of DRfold2 (right), respectively. Structures are rainbow-colored from 5β€² (blue) to 3β€² (red) end.

Accurate RNA structure prediction remains a challenge, despite recent computational advances. This study presents DRFold2, a #DeepLearning framework that significantly enhances accuracy of de novo #RNAstructure prediction by increasing contact prediction precision @plosbiology.org πŸ§ͺ plos.io/4aoOQiX

18.02.2026 09:37 πŸ‘ 24 πŸ” 8 πŸ’¬ 0 πŸ“Œ 0
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Ribosomal RNA expansion segments mediate the oligomerization of inactive animal ribosomes Cells down-regulate protein synthesis when stressed to conserve energy and shift resources toward repair. We found that in some mammalian cells, including neurons, stress also resulted in the formatio...

Out now in @science.org
Ribosomal RNA expansion segments mediate the oligomerization of inactive animal ribosomes | Science www.science.org/doi/10.1126/...

20.02.2026 11:06 πŸ‘ 56 πŸ” 23 πŸ’¬ 0 πŸ“Œ 0
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Selection of U-rich sequences reminds me of A-rich selection by the HUSH complex to silence sense transposons (I beleieve in non germ line cells). This also reminds me of how introns (at least in vertebrates) tend to be U-rich and exons A-rich (but short). www.tandfonline.com/doi/10.1080/...

18.02.2026 20:11 πŸ‘ 4 πŸ” 2 πŸ’¬ 1 πŸ“Œ 0

A Naïve RNA Sampling Core Enables Adaptive piRNA Specificity Against Transposable Elements https://www.biorxiv.org/content/10.64898/2026.02.07.704324v1

10.02.2026 05:17 πŸ‘ 15 πŸ” 11 πŸ’¬ 0 πŸ“Œ 2
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Advances in CLIP-derived methods have enabled high-resolution mapping of individual RNA binding protein-RNA interactions as well as RNA binding protein-associated RNA–RNA interactions #RNA #CLIP @evannostrandlab.bsky.social bit.ly/4bYjAsg

17.02.2026 16:25 πŸ‘ 17 πŸ” 10 πŸ’¬ 0 πŸ“Œ 0