David McQuarrie

Genetic evaluation of CRISPR-Cas9 off-target effects from deleterious mutations on Drosophila male single X chromosome
#Drosophila

SET1/MLL complexes control transcription independently of H3K4me3 Histone H3 lysine 4 trimethylation (H3K4me3) at gene promoters is thought to play a central role in gene transcription. H3K4 methylation is deposited by the SET1 (A/B) and MLL (1-4) multi-protein comp...

An early Christmas present for those interested in chromatin and transcription! Fantastic work from @au-ho-yu.bsky.social and @aleksszczurek.bsky.social . Thanks to Inge and Michiel for their help. Please repost!

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

High-throughput capture of actively transcribed region-interacting sequences reveals an intricate promoter-centered regulatory network Li et al. developed Hi-Coatis, an antibody- and probe-free method that employs Klenow polymerase to capture actively transcribed regions and their interaction loci. This approach simultaneously detects the activity of RNA polymerases I, II, and III and further reveals that repetitive elements exert regulatory functions in gene expression.

High-throughput capture of actively transcribed region-interacting sequences reveals an intricate promoter-centered regulatory network

Multi-region m6A epitranscriptome profiling of the human brain reveals spatial and temporal variation and enrichment of disease-associated loci - Nature Neuroscience Epitranscriptomic (m6A) profiling across five human brain regions and developmental stages uncovers region-specific and age-specific dynamics, preferential enrichment in disease-associated genes, and ...

Multi-region m6A #epitranscriptome profiling of the #human #brain reveals spatial and temporal variation and enrichment of disease-associated loci
doi.org/10.1038/s415...

The story of how multiple RBPs cooperate to repress translation is now out in @cp-cellreports.bsky.social by @marcopayr.bsky.social and in a great collaboration with @hennig-lab.bsky.social!

www.cell.com/cell-reports...

Transcription-induced mutation and gBGC at the Transcriptional Start Site impact the evolution of human protein-coding genes In the human genome, mutation rates vary along genes, yet their fine-scale structure and causes have remained largely unexplored. Here, we map mutations at single-nucleotide resolution, and uncover a ...

Our pre-print on the evolution of nucleotide content at the start of human protein-coding genes is finally out!

In this paper we demonstrate that the nucleotide content at the beginning of human protein-coding genes is greatly impacted by non-adaptive evolution.

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

Transcription start sites experience a high influx of heritable variants fueled by early development - Nature Communications The impact of transcription on germline mutagenesis remains poorly understood. Here, the authors identify a mutational hotspot at transcription start sites in the human germline that is significantly ...

We are not the only ones who see that transcription causes excess mutations at the TSS: www.nature.com/articles/s41...

Phosphorylation modulates secondary structure of intrinsically disorder regions in RNA polymerase II The intrinsically disordered C-terminal domain (CTD) of RNA polymerase II contains tandem repeats with the consensus sequence YSPTSPS and coordinates transcription and cotranscriptional events through...

Chen, W., Laremore, T. N., Yennawar, N. H., Showalter, S. A. (2025). Phosphorylation modulates secondary structure of intrinsically disorder regions in RNA polymerase II. J Biol Chem, 301(6):108533 www.jbc.org/article/S002...

Transcript-wide m6A methylation defines the efficiency of the cap-independent translation initiation https://www.biorxiv.org/content/10.1101/2025.11.25.690160v1

Analysis of Transcript Expression and Core Promoter DNA Sequences of Brain, Adipose Tissues and Testis in Human and Fruit Fly
#Drosophila

Finally out in @nature.com! We uncovered a mechanistic framework for a general and conserved mRNA nuclear export pathway. www.nature.com/articles/s41.... 1/

Functions of RNA m6A methylation at the molecular, genomic and organismal level: go.nature.com/484M6pB
Free to read here: rdcu.be/eR4zx

RNA stability enhancers for durable base-modified mRNA therapeutics - Nature Biotechnology A systematic screen identifies RNA elements that enhance the stability and translation of base-modified mRNA.

RNA stability enhancers for durable base-modified mRNA therapeutics go.nature.com/4opTAsV

m⁵C-Rol-LAMP, a simple qPCR-based assay, quantifies m⁵C RNA methylation at single nucleotides and uncovers stress-regulated rRNA modification in bacteria. #LMU_muenchen #lifescimunich #RNA #CRC1309 bit.ly/43AWnr4

Programmable initiation of mRNA translation by trans-RNA - Nature Biotechnology Translation can be initiated from a specific start codon using trans-RNA.

Programmable initiation of mRNA translation by trans-RNA - @cornelluniversity.bsky.social @iecb.bsky.social go.nature.com/3K7SEdO

The missing heritability question is now (mostly) answered Not with a bang but with a whimper

I wrote a little bit about the "missing heritability" question and several recent studies that have brought it to a close. A short 🧵

Ancient fossil reveals how plants and fungi first developed on land | Natural History Museum A new fossil fungus discovered in Scotland shows evidence of plants and fungi sharing nutrients to survive on land.

A new fossil fungus discovered in Scotland shows evidence of plants and fungi sharing nutrients to survive on land.

The fossil, more than 400 million years old, offers hints about the origin of one of the greatest partnerships in the history of life on Earth.

www.nhm.ac.uk/discover/new...

CRISPR-Cas–mediated heritable chromosome fusions in Arabidopsis The genome of Arabidopsis thaliana consists of 10 chromosomes. By inducing CRISPR-Cas–mediated breaks at subcentromeric and subtelomeric sequences, we fused entire chromosome arms, obtaining two eight...

CRISPR-Cas–mediated heritable chromosome fusions in Arabidopsis | Science www.science.org/doi/10.1126/...
Very nice work from Holger Puchta & colleagues

Looking for a PhD in RNA biology? The deadline is approaching fast! This is a great opportunity to do a PhD together with an industry partner fully funded by @nrpdtp.bsky.social BBSRC Case studentship.

Proteome-wide in silico screening for human protein-protein interactions Protein-protein interactions (PPIs) drive virtually all biological processes, yet most PPIs have not been identified and even more remain structurally unresolved. We developed a two-step computational...

Thrilled to share that the final piece of my PhD work is now on bioRxiv! biorxiv.org/content/10.1... With support from @nvidia and the @NSF, we used AlphaFold to screen 1.6M+ protein pairs, revealing thousands of potential novel PPIs. All data can be viewed at predictomes.org/hp

Single-nucleotide resolution mapping of m6A of zebrafish mRNAs in early embryonic development links m6A modifications to the maternal-to-zygotic transition https://www.biorxiv.org/content/10.1101/2025.11.19.688951v1

Adenine DNA methylation associated with transcriptionally permissive chromatin is widespread across eukaryotes - Nature Genetics Long-read sequencing in 18 unicellular eukaryotes reveals that 6mA is widespread across eukaryotes and is enriched at transcriptionally permissive regions, which are also marked by H3K4me3.

Out today, our take on 6-methyladenine #6mA evolution in Eukaryotes @natgenet.nature.com. We asked a simple question, is really DNA 6mA common across the eukaryotes? The answer is "yes" if you're a unicellular eukaryote 🦠, not so if you're multicellular 🐝🌱🍄. www.nature.com/articles/s41... 1/9

🦣🧬🦣🤯💥We are pleased to share our new paper about ancient RNA expression profiles from the Woolly Mammoth, now published in Cell @cellpress.bsky.social

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

If you want to know more, read the 🧵 below:

Sex-specific responses of small RNAs and transposable elements to thermal stress in zebrafish germ cells Environmental fluctuations influence heritable phenotypes through complex molecular mechanisms. In zebrafish (Danio rerio), the interplay between temperature variation, transposable element (TE) activ...

🚨 New preprint alert!
Our latest work from @immler.bsky.social lab 🐟🧬

Sex-specific responses of small RNAs and transposable elements to thermal stress in zebrafish germ cells

#TESky #TE #piRNA #miRNA #zebrafish #DanioDigest
🔗 Read here www.biorxiv.org/content/10.1...

A thread 🧵...

Nuclear-import receptors remodel the dilute phase to suppress phase transitions of RNA-binding proteins with prion-like domains. RNA-binding proteins (RBPs) with prion-like domains, including FUS, hnRNPA1, and hnRNPA2, assemble into functional, metastable condensates that organize ribostasis, but can also transition into self-t...

www.biorxiv.org/content/10.1... @rohitpappu68.bsky.social and Jim Shorter latest banger just dropped

Mapping chromatin structure at base-pair resolution unveils a unified model of cis-regulatory element interactions Li et al. apply base-pair resolution Micro Capture-C ultra to map chromatin contacts between individual motifs within cis-regulatory elements and reveal a unified model of biophysically mediated enhan...

Fine-scale chromatin mapping uncovers principles of cis-regulatory element interactions. #NBThighlight www.cell.com/cell/fulltex...

Control of gene output by intron RNA structure https://www.biorxiv.org/content/10.1101/2025.11.08.687378v1

RNA stability enhancers for durable base-modified mRNA therapeutics - Nature Biotechnology A systematic screen identifies RNA elements that enhance the stability and translation of base-modified mRNA.

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

Transposable elements are vectors of recurrent transgenerational epigenetic inheritance DNA methylation loss at transposable elements (TEs) can affect neighboring genes and be epigenetically inherited in plants, yet the determinants and significance of this additional system of inheritan...

Happy to share the results of a long-haul post-doc project, now online @science.org, aiming at understanding the rules of transgeneration epigenetic inheritance over TEs in plants and its extent and impact in nature. More below!
doi.org/10.1126/scie...

KATMAP infers splicing factor activity and regulatory targets from knockdown data - Nature Biotechnology A biophysical model uses knockdown or overexpression data to infer splicing factor activity.

KATMAP infers splicing factor activity and regulatory targets from knockdown data - @daspliceisright.bsky.social go.nature.com/47ycrMJ